Breast Cancer
Breast cancer is the second leading cause of cancer and death among women and accounts for 30% of female cancers in the United States. This year, 300,000 women and 2800 men will be diagnosed with invasive breast cancer.
Breast cancer development occurs when there is a disruption of normal breast cell growth and repair. Our body regulates and controls cellular balances by replacing damaged and aged cells, called apoptosis, with the generation of needed new cells. Cancer is able to alter this control and create an environment where uncontrolled rapid growth and replication occurs without regulation or cell death. In breast cancer, a significant factor in cancer’s initiation and proliferation is related to both specific endocrine hormones and growth factors which are hijacked by the cancer for its own advantage.
Ductal carcinoma describes the proliferation of cancer cells of the breast epithelial cells, which line the milk ducts while cancer that originates in the epithelial mammary glands is called lobular carcinoma. These are the two predominant forms of breast cancer
Seventy percent of breast cancers have hormone receptors that are present, termed Estrogen positive (ER+), and/or Progesterone positive (P+) , which directly impact breast cancer cell growth. In addition, ten percent of these hormone receptor positive cancers also have a cell growth stimulator called Epidermal Growth Factor (HER-2)+. Breast cancers can be categorized according to the presence or absence of these receptor types, and if positive afford a focus for treatments. There is also a layer of muscular cells in the breast tissue which are used to both move and help secrete milk but have no hormone or growth receptors. These are called triple-negative cancers.
These receptor pathways are critical factors in breast cancer initiation, as tumor cells divert control of these signaling pathways for tumor growth. However, these hormones and growth factors can be assessed in breast tumor tissue and there are treatments that can block cancer’s co-opting of these pathways to accelerate its own growth and spread.
Early diagnosis of breast cancer is becoming more common due to greater public awareness of mammography imaging, self breast exam and recognition of family hereditary risks. Diagnosing and treating early breast cancer, when localized to one breast only, has a 5-year survival of greater than 95%. However, when it becomes invasive to other local tissues, the five-year survival is 86%; and when it has spread or metastasized to distant areas, the 5-year survival is 28%.
So, while the goal is to achieve early diagnosis, it is essential for both women and men to be proactive in their preventive health and seek consultation when any of the signs that may be suggestive of breast cancer are recognized. See below
The initiation of breast cancer and its growth and progression can result from genetic hereditary mutations, passed through families, which alter the sequencing of the DNA. Most cancers, however, develop from alterations in genetic expression without genetic alterations to DNA.
This article will discuss and emphasize contemporary diagnostic testing and therapy strategies in breast cancer, recognizing their increased effectiveness in reducing progression and extending survival. The expansion of current knowledge, the new advances in genomics, and the use of innovative therapies using immune and targeted therapies are expanding and improving treatment options at lightning speed. Along with medical advances, integrating natural therapies for supportive care can improve and help restore quality of life during and after treatment.
Table of Contents:
Executive Summary
Breast cancer accounts for 30% of cancers in women in the United States.
Earlier diagnosis is occurring more frequently due to public awareness, preventive care with screening mammograms, self exam, and recognition and testing for hereditary risk factors.
With earlier diagnosis of local disease, the five-year survival rates are 90%. However, with invasive or distant disease, survival is shortened.
Ductal cancer involves the ducts that carry breast milk, while lobular cancer involves the mammary milk-producing glands themselves. These subtypes account for greater than 90% of all breast cancer.
Breast cancer initiation is related to heredity in 5-10% of cases.
The breast cancer 1 mutation (BRCA 1) is associated with ductal breast carcinoma, and the breast cancer 2 mutation (BRCA 2) is associated with ductal and lobular breast cancer.
BRCA1&2 genes act to repair DNA damage and these mutations inhibit that function.
Epigenetic effects, which change gene expression, are also associated with breast cancers and are linked to environmental chemicals
Many of these are considered estrogen mimics and increase the risk of growth of breast cells and initiation of cancer
These chemicals include:
Microplastics
Parabens
Pesticides
PFAS’s, which are water and stain-resistant chemicals
Other risk factors include advanced age, excessive alcohol and smoking, family history of a first-degree relative, a mother or sister with breast cancer, later age of childbearing, or no children.
Mammography includes:
Preventive screening mammograms at low levels of radiation.
Diagnostic 3D mammograms associated with abnormal imaging or exam.
Biopsy of abnormality is then performed as an outpatient procedure, with a needle biopsy to remove a tissue sample.
Common types of breast cancer are:
Localized Ductal carcinoma or Lobular carcinoma.
Invasive Ductal carcinoma accounts for 80% of breast cancer
Invasive Lobular carcinoma 10-15%
Uncommon, 1-2% of all other breast cancer
Paget’s
Inflammatory
Tubular
Papillary
Ductal and Lobular cancers, in situ, means localized in the duct or lobe.
If the biopsy does show invasive disease, surgery to remove the entire tumor and sample lymph nodes, sentinel node biopsy is then performed.
The Staging of the disease: Staging is a system that tells the physician, at the time of diagnosis, the extent of its presence within the body by using imaging, lab testing, and biopsy. This is clinical staging. After tumor removal, the microscopic staging done by the pathologist can give more precise information
Pathology of the tumor removed reveals:
The Grade or level of potential aggressiveness and growth
Hormone and growth receptor status
KI 67, rapidity of cellular growth
Tumor size, and whether the margins of removal are clear of tumor
Impingement of the tumor on local blood vessels or lymphatics, suggesting spread
Seventy-five percent of breast cancers have hormone receptors for estrogen and/or progesterone, as assessed from the biopsy, and are treated with hormone blockers to inhibit cancer growth.
Measurement of epidermal growth factor receptor-2 (HER-2) is also performed. It is positive in 20% of cancers and amenable to targeted therapies if present.
Risk Factors
Hereditary Risk Factors
There are specific types of breast cancer in which family heredity is known to directly influence causation. If you have a first-degree relative who has had breast cancer, it doubles your risk of developing cancer due to a potential inherited germline genetic mutation. The BRCA1 and BRCA2 genes are passed via hereditary and mutations in these genes raise the lifetime risk of breast I removed it duplication, and ovarian cancer, substantially, especially in younger women. These tumors tend to be of a higher grade with faster growth and do respond well to therapy. In a study spanning over ten years, men with these same BRCA1/2 mutations, found that one-third had some form of cancer, with many having either breast cancer or prostate cancer.
BRCA genes are needed for DNA repair after damage, often from ionizing radiation and these same mutations increase breast and ovarian cancer risk. If there is a positive family background for these potential cancers genetic testing is imperative. There are other less commonly inherited genetic mutations that can result in multiple organ cancers in which the breast is one of the targets in a constellation of disease.
Male breast cancer, while rare, occurs in 0.5-1% of the population with a higher incidence in older men. Their diagnosis is often at a more advanced stage, as there is less awareness that men can be affected, and limited recognition of the significant connection to family heredity. Men with a first-degree relative with breast cancer due to the BRCA mutation have a 20% risk of the disease themselves
Non-Hereditary Risk Factors
A strong associative relationship to breast cancer initiation appears to be associated with environmental toxicants. Many of them go unrecognized, as they occur in small amounts, accumulate over many years, and have few overt symptoms from exposure. Many studies view these initiating causes as creating messages that do not change the gene sequences of DNA, but rather gene expression or actions, which can potentially allow unrestrained cellular growth.
Greater than 80% of breast cancer is unrelated to inherited causes. Most oncologists believe that cancer’s origination is from damage to genes that can directly damage and alter the DNA, which allows uncontrolled growth and proliferation. Because the reasons this happens are unknown, preventive strategies appear difficult.
Endocrine Disruptors
They are a diverse group of chemicals that mimic estrogen and can bind to breast hormone receptor sites, and can decrease natural hormones, affect hormone release, production, transport, and elimination, and can interfere with normal elimination. These mimics can be found in pesticides, plasticizers, pharmaceuticals, personal care products, foods and their packaging and are also ubiquitous in the air, groundwater, packing materials and food additives, making them difficult to avoid.
A recent study, in 01/2024, found several hundred chemicals and provides an in-depth understanding of their exposure and their association to breast cancer.
Pesticides
In one of our referenced articles on pesticides there is a table of over 100 pesticides that can affect and disrupt endocrine hormones creating both imbalances and negative effects on the body, including glyphosate.
Glyphosate is an herbicide used worldwide and is the active ingredient in Roundup. It has been found in a variety of foods and is an herbicide sprayed on wheat, corn and soy. These grains are genetically engineered to withstand it.
DDT, DDE, which, while banned in the US for decades, still contaminates our groundwater and is still being used in other countries mainly for preventing malaria. Dioxin, while banned and not produced or used in the US, is a persistent toxin that can occur from the consumption of some animal and fish proteins being stored in our fat.
Microplastic Contamination
A recognized hazard of exposure to high levels of microplastic contamination is its direct effect on human health. The ubiquitous presence of these plastic molecules are considered persistent environmental contaminants.
Exposure to microplastics occurs from skin contact, inhalation via the respiratory tract, and ingestion of foods and beverages. It can systematically affect the body through the creation of chronic inflammation, mitochondrial energy dysfunction and reduced cellular protein production resulting in impaired immunity and organ injury.
Microplastics are also considered endocrine disruptors, chemicals that act as hormone mimics, increasing estrogen and androgens. There are many studies in humans and animals that report their association with the development of tumors. They are labeled xenoestrogens or foreign estrogens and act to alter genetic expression, epigenetically, by conveying information to breast cells that alter estrogen gene expression, stimulating excessive breast cell growth and cancer initiation. Elevated hormone levels from these foreign estrogens are also associated with ovarian, lung, prostate, and blood cancers.
Research studies also show that a number of types of microplastic molecules are capable of inhibiting breast cancer resistance protein and P glycoprotein, which cells use to pump out foreign substances.
A common exposure to this type of endocrine disruptor is
Bisphenol A (BPA), a Xenoestrogens found in synthetic chemicals used in plastic disposable water bottles, food wraps, and cash register tapes, and PCBs (polychlorinated biphenyls)
Also the mycotoxin from mold, Zearalenone, found in water damaged homes or businesses is a known endocrine disruptor that is similar to natural estrogen..
The use of microplastics continues to grow. Unsafe disposable plastic containers and bottles are used and disposed of. During the COVID crisis, the use of personal protective equipment, IV bags and tubing, and bottles of hand sanitizer containing microplastics was enormous.
While companies claim their products no longer have BPA, many have just changed to another molecule of bisphenol as a substitute, which is still dangerous. Glass and stainless steel water containers are available and safer for use.
Parabens
Parabens are endocrine-disrupting chemicals that are found in everyday items, being found as a preservatives in cosmetics, drugs, and even foods and pesticides. Exposure is primarily through personal care products and can be found universally in most products used on the face and hair; with Seventy percent of products containing this ingredient. They also have some estrogenic activity which remains on the skin as parabens inhibit the cell enzymes that would break them down.
Phthalates
These are endocrine disruptors that are also known to be associated with the development of breast cancer.
These chemicals are also commonly used as plasticizers, in food packaging and in daily exposure from personal care products, including deodorant, body lotion, hair care products and sunscreens. They are also used in nail polish to fervent chipping, vinyl used to make child toys softer and virtually all fragrances have them. However, in fragrances, many companies are allowed to not disclose their presence as they are trade secrets.
An article from 2024 reviewed the use of primary lotions, sunscreen, and oils in 4-8-year-olds, which showed significant urinary levels of phthalates, and information on the environmental working group website, ewg@ewg.org, indicates a link between phthalates exposure in early childhood and bone cancer. This website also lists safe products on their link called Skin Deep.
Triclosan
This is a lesser known chemical used as an antimicrobial in deodorants, shaving cream, shower gels and soaps and is a known endocrine disruptor and has estrogen properties.
PFAS, Per and Polyfluoroalkyl Substances
Are chemicals used in water-repellent clothing, stain-resistant fabrics and carpets, and some firefighting foam to create an environment that is waterproof, stain,grease, and heat-resistant?
It is also still found in food packaging and in groundwater contamination.
It is an endocrine disruptor and is associated, in high concentration, with the development of breast cancer.
Awareness
These toxins are recognized as potential initiators of cancer and its progression, as well as other complex chronic diseases. So, in discussing these toxicants, it is important, when possible, to avoid them, but the difficulty is in assessing the type and its sources.
Currently there are available sophisticated laboratory tests to define the types of toxins that might be present and the quantity. While the article discusses harmful endocrine disruptors, it is known that multiple environmental substances can influence the initiation of cancer by affecting immune function and tissue repair.
So it is also important to consider evaluating and treating other classes of toxic materials that might interfere with your healing and recovery as well as offer a potential to reduce the risk of cancer recurrence. When treatment is concluded and a person is considered cancer free, it doesn't mean that the causative initiators are gone.
The following recommendations are useful to assimilate into your life before, during and after breast cancer treatments.
Balanced nutrients in the diet are essential as poor-quality nutrients impair transformation of toxicants and make us prone to the downstream effects of inflammation which is oxidative damage
Genetic testing is easily accessible and can inform us of variants in detoxification pathways that often can be improved.
Lifestyle is always mentioned but do people sleep enough, laugh enough and relax enough
Is the GI microbiome working well? Both the Western and Chinese medical systems recognize the digestive system as the primary location of the immune system!
Are there hidden or lurking pathogens from infections like; Lyme, the herpes family, mycotoxins,previous pneumonias, Covid, or asymptomatic dental infections all of which stress and impair immune effectiveness.
Excessive electromagnetic exposures electronic devices.
For more information, the websites Environmental Working Group and Green Seal at http://www.greenseal.org offer help with product labels to reduce exposure. Think Dirty, http://www.thinkdirtyapp.com allows you to scan and see many products as to other possible chemicals you want to avoid and campaign for safe cosmetics; http://www.safecosmetics.org, connected to breast cancer prevention partners.
Other Risk Factors
Advancing age, with most breast cancer occurring after the age of 50
Early menstruation and late onset of menopause
Family history of a first-degree relative, mother, or sister
Never having a child, or having one after the age of 35
Depression, most likely related to imbalances in hormone pathways.
Alcohol intake of over 2-3 drinks/day increases risk by 20%: There appears to be an interrelationship in one pathway (CYP2E1) that is involved in breast cancer development and alcohol metabolism that suggests a connection to alcohol intake.
Smoking
There is an available tool called the Gail Model at http://bcrisktool.cancer.gov. This assessment can be accessed online and provides the risk of developing invasive breast cancer over the next 5 years, valid up to age 90.
It integrates your personal medical and reproductive background and your family history of a first-degree relative considered mother, sibling, or your child to provide a percent risk. It is valid for white and black women but is invalid in situations of a personal history of breast cancer or a known risk from a hereditary genetic mutation, BRCA 1&2, for example .
Diagnosis
Mammography
Overview:
The introduction of mammograms as a modern method of diagnosis only began in the 1960s, and it wasn’t until 1976 that the American Cancer Society officially recommended its use. Today, imaging is a cornerstone of breast cancer screening, and making an early diagnosis plays a crucial role in reducing invasive disease. In fact, twenty percent of breast cancer diagnosed in the United States is noninvasive cancer confined to the breast ducts, called ductal carcinoma in situ (DCIS) which commonly presents without a palpable mass. Eighty to 85% percent of these early cancers are found on a screening mammogram. Lobular breast cancer in situ is considered noninvasive and often found when biopsying for another reason, a lump or abnormal mammogram. However, it does increase the risk for invasive cancer.
The recommendation for screening currently recommends mammography for all women after the age of 40. Statistics indicate finding these lesions early, can prevent a significant percentage from progressing to invasive disease.
Male breast cancer can also be discovered using mammograms. The most common symptoms are a painless firm mass in the subareolar area and imaging is abnormal in 80-90% of cases.
Procedure:
Breast imaging, as a screening tool, involves two X-rays of each breast using very low-dose radiation And is often recommended as a part of annual preventive care. If a person has breast cancer symptoms or a distinct observation is made during the screening exam, a more detailed diagnostic mammogram can be performed. In addition, a radiology process called digital breast tomosynthesis, a 3D mammogram, can be performed, or using MRI imaging can be used in situations where the tissue is extremely dense and lesions can be difficult to see.
A recent study showed that women who were regularly screened for breast cancer, yearly, had a 47% lower risk of dying from the disease over 20 years. Yet even with mammograms and other imaging, life expectancy for women with undetected, or aggressive and metastatic disease has not changed.
Thermography
Thermography is a technique that uses sensitive infrared cameras to detect hot spots in the breast that might indicate malignancy or inflammation. It has a low sensitivity for cancer, less than 30%, and it doesn’t detect deep breast lesions; but the lack of radiation involved is a positive aspect. When used as a screening tool, any abnormality requires a mammogram for follow-up.
Ultrasound
Ultrasound is an additional technique that can be utilized to differentiate between cystic and solid lesions which cannot be determined by mammogram alone.
Breast self-exam
Breast self-exam (BSE) uses observation and self-exam for detecting breast abnormalities. Its value has produced diverse opinions about its effectiveness. Oncologists at Johns Hopkins state that BSE detects almost 40% of all breast cancers, while the Mayo Clinic states BSE is not shown to be effective in detecting or improving survival for women with breast cancer.
Another approach, recommended by the Gynecology Association of Specialists also doesn’t support BSE but recommends being observant of any change in breast size, pain, or contours with follow-up evaluation, by a specialist, when identified. Other concerning signs of persistent breast pain, any skin puckering or a dimpling appearance, a breast lump or fullness in the breast or armpit, changes in the nipple with soreness, discharge, retraction or inversion, redness, swelling, warmth, or heat in the breast. These suggest signs of early breast cancer until proven otherwise.
Biopsy
If a clinical exam reveals a suspicious mass or imaging reveals characteristics such as a distortion of tissue, calcium clusters, or a new mass at a previous biopsy area, a diagnostic biopsy is needed for tissue evaluation. Fortunately, while 80% of biopsies are negative for cancer the anxiety and fear they provoke can be overwhelming until a diagnosis is determined.
In performing a biopsy, the technique used to obtain tissue.is a fine, fine, or core needle aspiration procedure done by the radiologist using imaging as a guide. A sample of the total tissue is then removed. It can be done as an outpatient with just local anesthetic, with minimal pain and no scarring.
If the biopsy reveals DCIS, in a younger woman or someone with a strong family history of cancer, a referral for genetic counseling should be encouraged. Testing might reveal a significant genetic predisposition toward developing cancers, which might warrant consideration of a mastectomy rather than breast conservation therapy as a preventive measure. This was the decision made by Angelina Jolie when she learned she had the BRCA gene, which poses an 85% lifetime risk of breast cancer.
There is data to suggest that seeding of cancer cells is common after a diagnostic breast biopsy. However, data also suggest that in the long term, there are no significant adverse findings of local recurrence, distant spread, or overall survival.
However, many integrative practitioners recommend the use of the powdered form of the modified peel and pulp of citrus fruit called modified citrus pectin. There are studies indicating that this nutraceutical might reduce cancer cells from adhering to blood vessels. This might be a proactive step as a protective bridge in situations of needle biopsy. Its use, timing and dosage need an experienced practitioner to determine individually if it is appropriate
Liquid Biopsy
This is a recently approved blood test that can provide indirect evidence of several solid cancers, including breast cancer, by looking for circulating tumor cells and circulating tumor DNA. It is not indicated as an initial biopsy method for diagnosis but can be useful for people who have already been diagnosed with cancer but have metastatic disease, or whose current cancer therapy is not working. It is an easy blood test for tumor monitoring and the markers can offer individualized therapies and by comparison evaluate resistance to current treatment. Doing a single blood draw does not ensure success but if the results are positive, it is valuable.
There is an interview with Dr Robert Nagourney, an oncologist, that you can find here. This is an essential listening for anyone requiring cancer chemotherapies. His clinic and laboratory offer a unique approach to determining the cancer chemotherapy for a specific tumor, not the treatment that will stop tumor growth but what will kill the tumor. The tissue sample required is obtained in real-time from a surgical excision or a biopsy, packaged immediately, and sent to his lab for analysis.
Disease Staging/Grading and Pathology Info
Staging
Staging is a system that tells the physician, at the time of diagnosis, the extent of its presence within the body by using imaging, lab testing and biopsy. This is clinical staging. After tumor removal, the microscopic staging done by the pathologist can give more precise information. The international system for disease staging uses the initials TNM for categorizing the tumor, lymph nodes, and metastasis. Each describes essentially the anatomy of the cancer. T is the size of the tumor; N represents how extensive the spread is into regional lymph nodes, and M represents the spread through the blood to distant locations.
The information used in staging is based on this compiled information from clinical evaluations and treatments using history, physical exam, imaging and biopsies. Knowing this information provides a prediction of the progression of disease and helps guide treatment decisions.
Stages 1-3 indicate that the cancer is within the breast or lymph nodes, on that side. Stage 4 indicates that the cancer has spread outside the breast and nodes to distant locations, often to the liver or bones.
Grading
This involves the tumor tissue being viewed and graded by the pathologist under the microscope, on a scale from I-IV. The severity of the cancer is determined but how close the cancer cells are to normal. In Grade 1, they act more like the normal cells and as the grades go from 1-4, the cells change more and more with grade 2 & 3 showing less similarity to normal and stage 4 cells very abnormal and dangerous, meaning they are more likely to be more aggressive and grow and spread faster.
But besides the aggressiveness(grade) and location (stage), there are other parameters that are provided by the pathologist’s evaluation of the specimen or specimens.
Tumor size, the smaller the size, the better the prognosis
Are there tumor cells, microscopically, around the tissue lymphatics or small blood vessels, indicating greater risk of spread
What is receptor status, estrogen, progesterone and HER-2 to provide treatment options?
Was the tumor entirely removed or is there residual cancer present?
Is there a positive lymph node
Lab measurement of Ki67 determines the rapidity of tumor growth.
Integrating the totality of this information allows the determination of what degree of risk exists for further spread and the level and types of treatment that are required for a successful outcome.
Types of Breast Cancer
Breast Carcinoma in Situ
Breast carcinoma in Situ Implies the growth of cancer cells inside a milk duct, called ductal carcinoma in situ, DCIS, or if it is in the milk-producing glands, lobular carcinoma. But both are termed IN Situ, as there is no extension into the tissue around it. It represents 20-25% of all breast cancers which has increased due to the advent of mammography.
Treatment in DCIS consists of a lumpectomy, called breast-conserving surgery (BCT), or a partial mastectomy. After surgery, radiation treatment can be done in BCT, if the oncologist feels there is a risk of recurrence or spread, as it has been shown to reduce these recurrences by 50%. While It is the standard of care, if this risk based on pathology and genetic testing is very low it may be omitted. While studies show that length survival in BCS with or without radiation is very similar, the implication is that if omitted in a higher potential risk situation and the cancer does spread, it will require considerably more treatments with pharmaceuticals to achieve a longer length of survival. A discussion with your oncologist then becomes very important as each option provides long-term survival, but understanding your quality of life in each scenario needs to be understood. If radiation appears beneficial, consideration for radiation treatment allows a person to do what is necessary initially to reduce risk that can optimistically offer a high quality of life in the years to come and avoid recurrence. Is it worth considering?
See below for recommendation of endocrine therapy and possibly targeted therapies, in local or locally invasive disease, with the goal of preventing distant invasion and spread. Chemotherapy is indicated for treatment in situations of distant metastasis.
Invasive ductal carcinoma occurs in 80% of breast cancer diagnoses while invasive lobular breast carcinoma is often found to be invasive at the time it is discovered. Invasive implies the cancer has spread outside the duct or glands and can be local or may spread into the blood or lymph
nodes.
Lobular carcinoma, as mentioned, begins in the cells of the milk-producing glands. It is the second most common breast cancer, ocurring in 5-15% of women. It can be detected in 65% of patients on mammogram and while slow growing is often invasive when discovered. A high percentage are estrogen receptor + and can be treated with hormone therapy.
Inflammatory breast cancer occurs in only 1% but is the most aggressive and has the poorest prognosis. It blocks breast skin lymphatics and makes the breast red, swollen and inflamed. It tends to be seen in younger women and black women.
Paget’s Disease is a rare form of breast cancer that begins behind the nipple and extends into the areola.
Papillary breast cancer is also rare and begins in the breast duct and is invasive, but is more treatable than many invasive cancers.
Tubular carcinoma occurs in 2% of cancers, rarely spreads to lymph nodes and can be treated with hormone therapies as it is usually ER+.
Surgical Interventions
Breast cancer was recognized as early as the Egyptians, 3500 years ago. For obvious reasons, as cancers grew, lumps became visible on the skin surface unlike with many internal tumors. For an extended time however, little discussion about this disease occurred outside of medical literature, because of taboos and embarrassment, making diagnosis rare. It has only been the last 30 or 40 years that it has become openly discussed.
Breast surgery began in the mid-eighteenth century in France with the belief that removing the tumor could help in treatment. Later in that century, Dr. William Halsted assumed that cancer spread outward from the breast and could be cured by adequate removal of all local tissues. He performed radical mastectomies that involved the removal of a breast, the chest wall muscles under the breast, and local lymphatics. It was the operation of choice for almost a century until the 1970s when clinical trials demonstrated that less extensive surgery was equally effective using the modified radical mastectomy, which involved a segmental removal of breast tissue. Currently, a primary tumor is often removed via lumpectomy. Breast surgery for localized cancer is currently the best option for a cure when cancer is in an operable, accessible stage.
Advancement in medical knowledge has recognized that breast cancer spreads not only by advancing into local tissue but also via the lymphatic system or in the blood circulation, which can cause advanced disease and metastasis. In recognizing this limitation of surgery alone the strategy shifted from disfiguring surgeries to conservative surgery with systemic treatments if indicated.
With the diagnosis of breast cancer, removal of the diseased area or the breast itself is the next step to diminish the source of the cancer and reduce its risk of spreading. These choices and their contraindications should be discussed with your surgeon. It is important to know the outcomes of either breast-conserving therapy vs. mastectomy, but the decision about additional chemotherapy or radiation is dictated by the disease stages and grade of the disease.
Breast-Conserving Therapy
Breast-conserving surgery, or a Lumpectomy, can be an acceptable option for invasive breast cancer, but it is not an alternative for all people. There are several specific contraindications that can be discussed with your surgeon and the oncologist together.
Mastectomy
Mastectomy is the complete removal of tissue of the breast. In breast cancer, a therapeutic mastectomy is indicated for people who are not candidates for breast-conserving surgery and those who choose a prophylactic mastectomy to reduce their risk of cancer.
Simple mastectomy is the removal of the entire breast and the underlying connective tissue covering the chest muscles and as mentioned, has replaced radical mastectomy as studies showed that survival after either procedure was similar.
Modified Radical Mastectomy (MRM) involves the removal of the entire breast and fascia but in addition, involves the removal of the associated axillary lymph nodes. This procedure is utilized for people having biopsy-proven positive axillary nodes.
Breast Reconstruction
After mastectomy, breast reconstruction can be performed immediately or can be postponed until after the completion of other recommended treatments. This decision influences the type of surgery chosen. MRM and simple mastectomy are the techniques often recommended when delayed reconstruction is employed.
If immediate reconstruction is chosen as the treatment method, always consider whether chemotherapy or radiation will follow the surgery, as it can impair tissue healing during the reconstruction or further affect overall healing.
Immediate Reconstruction can be considered a treatment as well as a prophylactic measure. Surgical techniques can possibly be used to preserve as much skin as possible, and others can preserve the nipple-areolar area, offering the best cosmetic outcomes. This requires coordination between the breast and the plastic surgeon.
There are three types of reconstruction procedures available which are:
Devices called tissue expanders are placed for 1-3 months until the correct size is achieved and then another surgery will replace the expander with an implant. Most often, saline implants are used, but silicone is another option. Both are associated with a type of lymphoma, ranging from 1 person in 1,000 to 1 in 40,000 people, due to the outer surface material covering. Also, allergic reactions to the material can occur. Silicone is rarely used currently due to its association with the autoimmune disease Sjogren’s Syndrome. Implants will need to be exchanged after 10 years because of the incremental rise in potential rupture.
Autologous Based Reconstruction uses the patient’s own tissue for reconstruction. This procedure uses tissues from different parts of the body, including the thigh, abdomen, chest, or buttocks. The tissue flap feels more natural and gets bigger or smaller with weight changes.
Even with a flap, an implant may be needed to fill out the breast.
Total breast reconstruction uses fat removed from remote sites and injected into the breast area. This is chosen in situations where a person is not a candidate for other procedures or chooses not to use other available choices.
There are also patients with hormone receptor status who are poor surgical candidates due to medical risk that some oncologists are treating with a hormone blocker without surgery, hoping for some benefit. While not curative, it may slow disease progression.
Sentinel Nodes
The burden of disease in the axilla and armpit area is significant and related to the ultimate prognosis. Pathological tissue evaluation using surgery accurately defines advanced lymph node disease, while clinical exam alone will miss twenty-five percent of cases.
Initial evaluation of the axillary nodes for diagnostic purposes samples specific nodes. Marking these nodes involves injecting a dye under the skin of the breast where it enters the lymph channels that drain the breast. The nodes that are observed to be the first ones receiving tracer, called the sentinel nodes, are then removed, and evaluated. These are the gateway nodes to the axillary node complex of the breast, and if they are negative, then the others are also negative. If the sentinel nodes are positive, then the other nodes will be surgically removed, followed by local radiation. Performing sentinel node axillary biopsy potentially avoids future problems with over or undertreatment, and if negative reduces the risk of more tissue damage.
An oncologic physical therapist specializing in rehabilitation following breast cancer surgery is extremely beneficial. These are expert caregivers who can help improve upper arm strength and swelling, increase range of motion, and decrease pain. Their individual exercise plan can also help reduce scarring and lymphedema and improve tissue circulation and flexibility in preparation for reconstruction.
Additional Treatment Options
Radiation Therapy
In breast cancer, radiation therapy uses high-energy particles that disrupt cancer cell DNA to prevent it from dividing and growing so that they die. Normal cells in the area are also damaged but regenerate over time and grow again. It provides a direct treatment in a localized area which differs from chemotherapy, which can affect the entire body.
Radiation can be used:
Prior to surgery to reduce tumor size
After surgery to help prevent recurrence by destroying residual tumor cells.
In palliation for tumors that are pressing on nerves, organs and bone tumors.
In situations where women require a mastectomy due to greater disease burden, radiation is utilized if the cancer has spread to the chest wall or lymph nodes.
Radiation therapy is provided by a team: a physician trained in radiation treatments, specialists trained to determine machine operations, exact dosages, planners, people to administer your treatment, and a nurse to provide follow-up and management of side effects.
Women treated with breast-conserving surgery, or lumpectomy, are often recommended for adjuvant radiation therapy as part of their local treatment, rather than surgery alone. However, this recommendation is not advised for women >65 years with ER+, HER- and no positive nodes, as data suggests that radiation therapy does not provide an overall survival benefit.
Treatments historically are 5 days a week for 5-6 weeks, but at some centers breast irradiation is completed in 1-4 weeks and partial breast radiation in only several days.
In situations where chemotherapy will be used after surgery radiation is performed after its completion; whereas in situations where hormonal therapy is to be used, radiation is performed during treatment or even prior to its initiation.
The following recommendations Enhance effectiveness of radiation therapy:
Avoid sugar entirely. Try to maintain a low glycemic diet. High-sugar diets stimulate a hormone called insulin-like growth factor 1 (IGF-1) which is said to reduce sensitivity to radiation.
Specific lifestyle and nutritional recommendations can improve outcomes and reduce side effects when provided by an experienced practitioner. Niacinamide, vitamin B3, enhances the effect of tumor damage due to radiation with minimal effects on normal tissue.
Curcumin appears to increase sensitivity to radiation therapy and diminish the severity of skin inflammation.
EGCG reduces the severity and incidence of radiation dermatitis when given orally. Also, when mixed with water and applied topically it reduces itching and irritation.
Side Effects of Radiation
The most common side effects of radiation are generally localized skin reactions in the radiation area. These include skin redness, burning and pain, itching, changes in pigmentation, and local swelling. Using non-oil-based creams, as oils can cause burns and should be avoided. Topical creams such as calendula alone or when mixed with Traumeel cream, can be used for milder skin reactions. A Chinese ointment called Lithospermum ointment is also an excellent remedy, but it stains clothes. In situations where the tissue blisters and peels, more specific medical treatment will be needed.
Systemic Effects related to radiation can include nausea, vomiting, malaise, diarrhea, headache, fever, and sweats.
Another expected effect of radiation is the gradual increase in fatigue levels. In the early stages, fatigue will seem to minimally affect overall energy. But as the weeks go by, it will increase substantially, as the cumulative dose of radiation increases. Post-radiation recovery is often slow, and patients need to be prudent with energy expenditure by pacing activities and increasing rest periods. Without these self-care measures, healing and fatigue can be prolonged.
Gene Expression Assays
Genetics is the study of single genes related to heredity while genomics looks at the whole genome and information provided by genetic patterns.
Oncotype Dx is one of the several available genomic profile tests in breast cancer that allow for precision treatment in early-stage estrogen receptor + tumors without nodal disease. This one assesses 21 genes, from an individual’s breast cancer tumor sample, and provides a quantitative score from 0 to 100. Lower values identify 70% of women with early-stage, node-negative breast cancer, who would receive no benefit from chemotherapy, as well as the 30% of women who would. It also predicts the 9-year risk of distant recurrence in node-negative disease.
While not a genetic test, the nuclear antigen, Ki67, is a protein marker of active cell proliferation, or the rate of growth, of tumor cell populations. It is strongly associated with prognosis and outcome and included with other testing in treatment decisions.
Pharmaceutical Therapies
Hormone Therapy
Targeted Therapy
Immunotherapy
Cytotoxic Therapy (Chemotherapy)
Adjuvant therapy is the name of additional treatment for cancer commonly given after the initial surgical and radiation treatment, to reduce the risk of recurrence, while neo adjuvant is given before the main treatment, often surgery, to shrink the tumor.
Clinical studies and research have defined precise targeted therapies based on specific breast cancer cell receptors. If a subtype has potential receptors, specific treatments are available that can block the cancer’s growth. These patterns include: Estrogen (ER)
Progesterone (PR)
Epidermal growth factor (HER2)
Positive hormone receptors occur in approximately three-quarters of breast cancers. These are estrogen-positive (ER+) and progesterone-positive (PR +). If not present, they are called ER- or PR - .
The human epidermal growth factor receptor (HER-2) is found in 15-20% of breast cancers, and when genetically overexpressed stimulates breast cancer growth. If the receptor is + it is called HER2+, and HER2- if not present.
Luminal A subtype is defined as Estrogen receptor positive (ER +) /progesterone receptor positive (PR +) and human epidermal growth factor receptor negative (HER-2-) and low KI 67 (proliferating cell nuclear antigen), indicating the rapidity of cancer cell growth. Luminal cells are the epithelial cells lining the ducts and lobules in the breast. This pattern is seen in 65-75% of invasive cancers, but they tend to be less aggressive, slower growing and have a more favorable prognosis due to these receptors, as hormone therapies can be used to block their actions.
Luminal B subtype is defined as ER+/PR+ /HER-2+. It expresses estrogen progesterone receptors or both and is HER 2+ or highly positive for KI67 which is indicative of an actively growing tumor. It has a poorer outcome than Luminal A. This pattern is also responsive to hormone treatment as well as epidermal growth factor blocking drugs.
Triple Negative Breast Cancers (TNBC) lack estrogen, progesterone, and epidermal growth factor receptor 2. It occurs in approximately 15-25% of women and are aggressive, highly invasive, and have a poor prognosis. It is seen more commonly in younger black and brown women or in older and younger women with BRCA1/ 2 mutations. If triple-negative cancer is found, BRCA mutation should be done as it influences the type of treatment but also signals the need for the surveillance of family members.
Because the disease is often more advanced when discovered, relapse is common, and overall survival is markedly decreased compared to other breast cancers that have specific targets for treatment.
Hormonal Drug Therapies
Selective Estrogen Receptor Modulators (SERMS): Tamoxifen (Soltamox), Evista (Raloxifene)
These are drugs that can block estrogen’s effect on breast cancer cells that are estrogen receptor positive. They are used in treatment of women with premenopausal breast cancer, as they are still producing estrogen via ovarian stimulation. It also has benefits for prevention of breast cancer, called chemoprophylaxis, in high-risk women, and in post-menopausal women with DCIS who are unable to tolerate aromatase therapy.
In women with ER+ and DCIS, tamoxifen can lower the risk of the cancer returning or becoming invasive and also can prevent DCIS and LCIS (Lobular) , while Evista can raise the risk of DCIS.
In ER+ invasive disease tamoxifen can lower the risk of recurrence and extend survival as well as reducing cancer occurring in the other breast.
Side effects:
The most common side effects include:
64% experience flushing
32% experience fluid retention,
30% experience vaginal discharge
30% experience Irregular cycles
26% nausea
19% experience skin changes,
Serious side effects that occur less commonly are blood clots, cataracts (tamoxifen only) and in premenopausal women diminished bone density.
Tamoxifen has a serious risk of uterine cancer, with Evista having a third less risk and a lower risk of blood clots but the cardiovascular and stroke risk were the same
Supportive Supplementation to Enhance the effectiveness of tamoxifen
Green Tea extract and Soy are synergistic
Melatonin
Acetyl-L Carnitine
CoEnzyme Q 10
Indole-3-Carbinol works on a separate signal inducing pathway to suppress breast cancer growth
Avoidance while on Tamoxifen
Curcumin can inhibit the enzyme that activates tamoxifen and may reduce its effectiveness
St John’s Wort can increase the enzymatic breakdown of tamoxifen more quickly
Black Cohosh
Menopausal symptoms will commonly develop in premenopausal women associated with hormone receptor blocking and can be extremely bothersome and can be successfully and safely addressed by practitioners of Chinese medicine.
Predict Breast Cancer was developed by the University of Cambridge and The National Cancer Registration and Analysis Services in the UK. Studies of thousands of women with invasive breast cancer have used the factors of tumor size and type at diagnosis, nodal involvement, and receptor status of estrogen (ER), HER-2, and Ki67 to determine the benefits and outcomes of hormonal and chemotherapy treatments.
Using this information for statistical analysis has allowed correlations to be made as to the average likelihood of over-survival and how much benefit, on average, might be seen using different treatments. It is, however, unable to predict a single individual’s survival.
Aromatase Inhibitors (AI): Femara(Letrozole), Arimidex (Anastrozole), Aromasin (Exemestane)
These drugs lower estrogen levels
Aromatase is an essential enzyme for the conversion of androgens, C19 steroids, into estrogens. These inhibitors are used only in postmenopausal women by blocking the enzyme aromatase, which converts androgens to estrogens at extra-ovarian sites. After menopause, while estrogen production is markedly diminished, other organ systems like the adrenals, pancreas, and adipose tissue can still produce estrogen. So, to diminish this production, these drugs block conversion to estrogen.
Side effects:
Side effects also include:
50%, hot flashes
24%, sweating
53%, elevated cholesterol
22%, osteoporosis and fracture
20%, muscle and joint pains
15%, altered menses
13%, depression
19%, fatigue
11%, rash
The side effects of decreased estrogen are, again, menopausal symptoms such as night sweats and hot flashes, vaginal dryness and decreased libido, and emotional fluctuations.
The following supplements have been shown, when tested on living breast cancer cells in the laboratory, to potentially offer value in treatment.
Studies using breast cancer cells demonstrate that melatonin acts as an aromatase inhibitor, decreasing the production of estrogen by regulating gene activity that normally promotes aromatase.
Grape Seed Extract has been shown in the lab to act as an aromatase inhibitor to prevent the conversion of androgens to estrogen. It is also known to inhibit or decrease estrogen production by inhibiting the aromatase enzyme.
DIM also acts as an aromatase inhibitor.
Vitamin D supplementation, especially when the Vitamin D level is low, can improve aromatase-induced muscle and joint pain symptoms, as can acupuncture.
Selective Estrogen Receptor Down Regulators (SERDs): Faslodex (Fulvestrant), Orserdu (Elacestrant)
These drugs bind to estrogen receptors so tightly they degrade the receptor to prevent the tumor cell from being able to use estrogen to mediate growth. It is used in advanced disease or metastasis.
Side effects:
Side effects of Faslodex can include:
34%, nausea
24%, diarrhea
83%, low WBC
53%, lymphocytes
18%, vascular dysfunction and possible heart failure.
16%, bone pain
17%, rash and hair loss
47%, increased risk of infection.
Hot flashes, and myalgias but most prominently, digestive issues.
Liver inflammation and elevated cholesterol can also occur.
Targeted Therapy, Used in Combination With Hormone Therapy
Hormone therapies are very effective in inhibiting the role of estrogen receptors in breast cancer. However, 20% of patients have resistance to endocrine therapy or become resistant to it over time. The addition of these drugs below can enhance hormone therapies but can result in additional side effects.
Kinase Inhibitors Therapy in Women With ER+ Disease
Adjuvant CDK 4/6 or Cyclin-Dependent Kinase Inhibitors in ER+ disease:
Ibrance (Palocicib), Verzenio (Abemaciclib) Kisqali (Ribcicib), are kinase inhibitors, kinase inhibitors can often be recognized with their (ib) suffix.
Cyclin Dependent Kinase Inhibitors target the communication within the cell’s internal messaging system. These communications determine what would be considered the requests and jobs needed to be done within a cell. These drugs specifically interrupt the signals of communication that stimulate cancer growth. These drugs can also be given with an AI drug or the SERD drug, Faslodex.
It is used for patients who have large lesions, multiple positive lymph nodes and are therefore at a higher risk of recurrence.
A recent study of hormone therapy in HR+ /HER 2- with Verzenio, for example, showed that breast cancer patients with a high risk of recurrence had a 37% decrease in recurrence or death.
Side Effects
Side effects of Ibrance can include:
81%, Lowered neutrophils and Lymphocytes
83%red cells
60%, Low platelets
83%, low red cells
37%, Fatigue
33%, Hair Loss
30%, Nausea and stomatitis
Side effects of Verzenio include:
80%, Diarrhea
90%, Elevated Kidney function
40%, Elevated liver function
82%,Low white cells and anemia
Side effects of Kisquali include:
40%, Nausea
90%, Elevated liver functions
36%, Musculoskeletal pain
36%, Fatigue
mTOR (Mechanistic Target of Rapamycin) and PI3K Inhibitors
Both of these drugs are components of the same pathway that regulates cell survival and growth under normal conditions but in cancer when overactive it reduces normal cell recycling, autophagy, and apoptosis or programmed cell death associated with aging or damage. This pathway is overactive in 70% of cancers.
Afinitor (Everolimus) is an oral pill used in postmenopausal women having increased cancer growth while already being treated with aromatase inhibitors, Arimidex or Letrozole and with advanced disease. It also may stop the tumor from developing new blood vessels.
Side effects
Side effects of Everolimus include:
92%, low red blood counts.
58%, decreased white blood cell counts.
78%, stomatitis
30+%, nausea, vomiting, constipation or abdominal pain.
45%, fatigue
59%, rash
50-60%, liver enzyme abnormalities
Pi3K Kinase Inhibitors
Piqray (Alpelisib) blocks the cell growth stimulator called PI3K. Approximately 30-40% of breast cancers have this positive gene mutation. If you are ER+ and HER 2- and have advanced disease while being treated with or after treatment with an aromatase inhibitor, a serum estrogen receptor blocker, Piqray can be used for treatment.
Side Effects
Side effects include:
52%, severe skin reaction
85%, diarrhea 85%
79%, elevated glucose
Antibody-Drug Conjugate
Trodelvy (Sacituzumab Govitecan) is another example of a monoclonal antibody but combined together with a chemotherapy drug for advanced ER+ and HER2- breast cancer. The monoclonal antibody acts to hone and attach to its target a protein called Trophoblast cell-surface antigen 2 (TROP2), which is overexpressed and causes cancer growth. The chemotherapy is then able to directly attack the cancer cell. This drug is also used in advanced disease in women who have been on hormone therapy and at least two chemotherapies.
Side effects of Trodelvy include:
84%, low neutrophils and lymphocytes counts.
69%, decreased red blood cell counts.
69%, diarrhea
Targeted Therapies for Her 2+ Breast Cancer
These drugs downregulate the oncogenic protein, HER 2, which stimulates breast cancer growth. It is a monoclonal antibody, but it does not specifically activate the immune system but rather binds to that HER 2 receptor to inhibit its action.
In Breast cancer, 15-20% of women overexpress a cell protein called Human Epidermal Growth Factor Receptor (HER2). Having this positive receptor tends to make these cancers grow and spread more aggressively than patients who lack this receptor. Treatment to stop the amplification of growth rely primarily on the manufactured monoclonal antibodies, Herceptin (Trastuzumab) or Perjeta (Pertuzumab). It is surmised that they bind to the receptors to fight tumor growth by signaling the cell to stop growing or signaling the immune system to destroy the cell.
Herceptin (Trastuzumab)
It can be used prior to surgery, called neoadjuvant therapy, or after surgery, called adjuvant therapy, as HER2+ treatment. The duration of treatment is usually 6 to 12 months and is indicated in both early and advanced disease in combination with chemotherapy or as a stand-alone drug following chemotherapy. In situations where diagnosis is made early, chemotherapy combined with a targeted antibody directed at the HER2 protein, improves survival by almost 90%.
Treatment for HER2 + patients that are at higher risk are being given a combination of two immunotherapies, Herceptin (Trastuzumab) and Perjeta (Pertuzumab combined with cell-destructive chemotherapy. In recent studies, this combination extended disease-free survival.
Breast cancer cells that do not have the HER2 receptor (HER2-) do not benefit from these adjuvant therapies. However, because they do not have this growth hormone overexpression, they are slower growing with a reduced likelihood to reoccur and spread.
Other cancers also have HER2+ receptors which increase their growth, including the pancreas, bladder, ovary, and current treatment for advanced stomach cancer does utilize Herceptin. New categorizations of cancer based on cancer cell receptors continue to expand the connections between cancer types rather than their differences. In the future, cancer will most likely shift to this framework of treatment classification. Your diagnosis will be based on the markers for treatment and secondarily on the organ.
Side Effects
Side effects of Herceptin (Trastuzumab)
47%, pain
36%, chills and fever
22%, abdominal or back pain
25%, vomiting or diarrhea
26%, cough
18%, rash
Antibody-Drug Conjugates (ADC)
Just as with ER+ drug conjugates these conjugates connect a HER2 monoclonal antibody to a chemotherapy drug allowing both to work together, directly on the cancer cell. So rather than the chemotherapy circulating in the blood to engage the cancer, it is brought directly to it.
Kadcyla (Ado-Trastuzumab Emtansine)
This combination combines Trastuzumab and the cytotoxic drug Emtansine for use in early disease; when after surgery if the drugs were given individually but hadn’t eradicated the tumor, this conjugate can be given. Or in advanced cancer for similar circumstances; individually they had not eliminated the cancer.
Side Effects
Side effects of Kadcyla include:
50%, fatigue
31%, low platelets
42%, nausea
36%, musculoskeletal pain
Potential serious hepatotoxicity
22%, decreased cardiac function
Enhertu (Fm-Trastuzumab Deruxten)
Another HER2 antibody chemotherapy combination is used in situations where surgery can be used or in advanced disease when the initial HER2+ drug has failed to eliminate the disease.
Other Serious Side Effects of HER-2 Drugs and Integrative Recommendations
These drugs can cause heart damage and its complication, heart failure, during treatment and even after therapy is completed.
They cause heart dysfunction in 15% of people, decrease the heart's output in 44% and cause heart failure in 28%. Usually, the effects are not long-lasting and improve when the drug is stopped. However, the risk of these side effects is increased with the use of chemotherapy drugs like Ellence (Epirubicin) and Adriamycin (Doxorubicin) which also potentially cause irreversible heart damage.
Having other conditions such as obesity, hypertension, being 50 years or older, and existing heart issues can further increase risk.
Regardless of these potential risk factors, all patients are evaluated with either a MUGA scan or echocardiogram prior to and throughout treatment to determine any abnormal changes in cardiac function that require intervention.
Supportive treatments
Supportive care to help reduce the risk from chemotherapy drugs that cause cardiac damage reflects protection of the energy-producing cells, the mitochondria in the heart. Mitochondria are organelles within the cell whose biological function is to create energy. It is believed that the HER-2 drugs reduce this functional ability, thus reducing the strength of the heart’s pumping action.
Taking these supplements, in relation to cardiac dysfunction requires an experienced integrative practitioner.
CoQ10 should be administered during chemotherapy with these drugs. It has been shown to prevent cardiac toxicity by reducing oxidative stress to the mitochondria.
Resveratrol also protects the mitochondria from oxidative cardiac muscle cell damage
L -Carnitine reduced doxorubicin cardiotoxicity
Hawthorn Berry has been used in heart failure, but no evidence suggests it is effective in chemotherapy-induced heart failure.
Grapeseed extract also helps protect against chemotherapy-induced cardiac dysfunction
Kinase Inhibitors For HER 2 + Breast Cancer
HER 2 is a kinase protein that transmits messages to tell cells to grow. The kinase inhibitors block that signaling.
Tykerb (Lapatinib) – is an oral pill taken daily. It is used to treat advanced breast cancer and is typically given with Trastuzumab and capecitabine, a cytotoxic drug.
Side effects (when used in combination)
Side effects of Lapatinib include:
44%, Diarrhea, and nausea
44%, Rash
45%, Elevated liver tests
56%, Low hemoglobin
Nerlynx (Neratinib) -This is also an oral drug that is given for one year after Trodelvy include:
84%, low neutrophils and lymphocytes counts.
69%, decreased red blood cell counts.
69%, diarrhea
Tukysa (Tucatinib)-This is a twice-a-day pill used in advanced breast cancer after using another HER 2 targeted drug and is combined with Trastuzumab and capecitabine.
Side effects
Side effects of Tucatinib include:
95%, Diarrhea
53%, Nausea
63%, Hand & Foot syndrome rash
35%, Loss of appetite
Targeted Therapy for Women With BRCA Gene Mutations
Women with BRCA mutations inherit them, they are present at birth. Most mutations that initiate breast cancer occur during life, are not present at birth and not inherited. The function of the BRCA gene is to help repair damaged DNA throughout the body. There are other repair proteins that are also able to repair damaged DNA. One is the PARP protein, poly (ADP-Ribose) polymerase that acts by a different mechanism to repair damaged DNA.
Treatment consists of using drugs that inhibit this PARP repair mechanism. The idea is, that since breast cancer cells have one problem with repair because of the BRCA gene, the blocking of a second one makes the cancer cells even less likely to be able to repair themselves, so they die.
Lynparza (Olaparib)This drug is utilized in early-stage breast cancer for patients that have the BRCA gene are HER2 negative and have had chemotherapy prior to surgery or after because they are at high risk of the cancer reoccurring. It can improve survival. It is also used in advanced and metastatic disease.
Side Effects
Side Effects of Olaparib include:
60%, nausea
55%, fatigue
36%, anemia
20-30%, digestive issues
Talzenna (Talazoparib)
This drug is used in women with a BRCA mutation, are HER2 negative and have advanced or metastatic disease and have already had chemotherapy. In women with hormone receptor + disease it can be used in women who have had hormone therapy.
Side Effects
Side effects of Talazoparib include:
25%, alopecia
53%, low white counts
27%, low platelets
35%, elevated liver functions
49%, nausea
A rare side effect of these drugs is a 1.5% risk of blood cancers called myelodysplastic syndrome or acute myeloid leukemia. However, if it occurs, it carries a 50% mortality.
The BRCA 1 gene, as mentioned, is involved in the repair of chromosome DNA damage. These breaks contribute to the development of cancer. The supplement Selenium was shown to reduce this breakage and should be considered as a preventive measure in BRCA1 people.
Triple-Negative Breast Cancer (TNBC) Treatment
Triple-negative breast cancer, TNBC, is a subtype indicating an absence of estrogen, progesterone, or HER-2 receptors, and so is not sensitive to hormone or HER2 treatments. This subtype also has no definitive treatment protocols, so treatments rely primarily on chemotherapy. It represents 15-20% of breast cancer and develops mostly in younger women, <40, who are premenopausal. Studies show it to be highly invasive, prone to metastasis and relapse and has a poor prognosis.
Tissue gene expression in TNBC revealed six subtypes, with such the cancer influencing: cell cycle regulation, DNA repair, stem cell activation, enhanced hormone signaling, cancer cell migration and immune dysregulation.
Reviewing the regimes for treatment all entailed the use of three different classes of cytotoxic drugs and even with neoadjuvant treatment before breast surgery there is a high relapse rate.
The goal is to connect many of these genetic subtypes with more targeted chemo regimens, as research continues to discover better more effective treatments.
Antibody-Drug Conjugate
Trodelvy (Sacituzumab Govitecan) is another example of a monoclonal antibody but combined together with a chemotherapy drug for use in TNBC. The monoclonal antibody acts to hone and attach to its target a protein called Trophoblast cell-surface antigen 2 (TROP2) which is overexpressed and causes cancer growth. The chemotherapy is then able to directly attack the cancer cell. This drug is also used in advanced disease in women who have been on hormone therapy and at least 2 chemotherapies.
Side effects
Side effects of Trodelvy include:
84%, low neutrophils and lymphocytes counts.
69%, decreased red blood cell counts.
69%, diarrhea
There are significant clinical trials with combinations of antibody-chemotherapy protocols and checkpoint inhibitors both in metastatic breast cancer and triple negative disease. There has been some sucess, but long lasting responses are limited except in a small subset of women.
Common Chemotherapy Protocols
Many of the subtypes use multiple cytotoxic drugs combined with targeted therapies such as mTOR, PARP inhibitors or growth inhibitors , while some types use multiple targeted therapies
Some of the classes of cytotoxic agents used in TNBC combinations:
See appendix for side effects
Alkylating agents- Cyclophosphamide
Anthracycline Blockers – Doxorubicin
Antimetabolites- Fluorouracil
In Advanced disease: Often combinations of chemotherapies are utilized:
Antimetabolites -Gemcitabine or Capecitabine
Antimicrotubular -Taxanes
Antimicrotubular (Non Taxane)-Eribule
DNA cross link interference -Platinum
If cytotoxic chemotherapy becomes a chosen therapy, its effects are designed to be administered via an IV infusion that travels in the bloodstream to the cancer cells, stops them from dividing, and kills them. Like other cancer therapies it is designed to reduce your risk of recurrence and extend life; but the effectiveness of this approach is often dependent upon how far the cancer has spread or metastasized. This form of treatment is often chosen, usually after an initial treatment involving hormones or targeted therapies.
Prior to the infusion, given by the oncologists, a pre-administration evaluation is needed each time to ensure potential complications are addressed. Adequate hydration prior to and at the infusion center is essential. Lab testing is done prior to treatment, and sometimes, based on values, dosage adjustments for the drug are made. There are also medications given prior to the infusion, often to prevent nausea and vomiting and reduce the risks of allergic reactions. An issue related to this allergy prevention of a potential drug reaction is the large dose of steroids given prior to infusion. While needed, recognize that this medication will uniformly “wire you up” and will likely interrupt normal sleep for a few days. In addition, stimulators of white and red blood cells sometimes will be needed as the chemotherapy can decrease white blood cell counts needed to help protect against infection or increase the red blood cell count if anemic from treatment.
Preparation for Cytotoxic Chemotherapy
Among integrative practitioners, limited studies suggest that short-term fasting may increase the effectiveness of chemotherapy therapies while reducing their side effects and toxicity. Fasting suggests a protective effect on healthy cells and a reduction in the expression of some genes that increase cancer growth. It also reduces insulin-like growth factor (IGF-1) and blood sugar, both of which encourage cancer growth. Fasting also reduces damage to white blood cells as well as fatigue and GI side effects.
Those desiring Short-Term Fasting (STF), during cancer treatment, need an experienced practitioner to guide them. Experienced clinical assessment and monitoring of weight, BMI, body composition, and appropriate laboratory testing are required to achieve minimal health risk. Those with significant cardiovascular or renal disease, who are pregnant or breastfeeding, are underweight, or have an eating disorder, uncontrolled diabetes, dementia, or psychotic episodes are not recommended for STF.
Most studies related to STF are based on middle-aged patients, so there is little information on how the elderly or young adults tolerate fasting. Commonly expected symptoms include nausea, upset stomach, headache, fatigue, insomnia, and achiness. Those with preexisting medical problems need to be monitored for any changes in signs or symptoms. So far, the data suggests that the time frame involved is 24-36 hours prior to chemotherapy and 24 hours post-treatment. Initially, the length of time of the fast is shortened to assess how well it is tolerated.
Lifestyle Modification for Reduction of Risk and Improved Survival
Breast cancer incidence has increased over the last twenty years. While diagnosis and treatment modalities are improving, knowing what lifestyle revisions can reduce both disease initiation and recurrence risk seem imperative and crucial. This discussion will focus on general nutritional recommendations, physical activity and exercise and obesity.
Dietary Suggestions
There are many opinions regarding what constitutes beneficial and optimal nutrition during and after cancer treatment. Consideration of personal choices, cultural background, financial affordability, and availability of foods and markets often determines not only individual but family dietary possibilities.
Recognizing the effects of quality food and balanced nourishment as treatment modalities supports current knowledge of its ability to reduce side effects of treatment and accelerate recovery and, after treatment, its ability to restore energy and reduce fatigue, strengthen and add resilience to the immune system, and promote the prevention of recurrence. Related benefits can also be expected by moderating alcohol. Avoiding empty, high-calorie, sugary foods and drinks, restricting the intake of food additives and chemicals, and overindulgence in fast-food meals. Combining these approaches offers flexibility without rigidity with the goal of your long-term survival rather than following the perfect diet, because there isn’t one.
During chemotherapy and radiation, just to feel like eating can be difficult. Getting to the store to shop and preparing meals can be an energy drain. So enlisting assistance and even home food delivery can be an asset. Using clean quality protein and /or collagen powders mixed with organic nut, dairy, or goat milk offer easily digestible and assimilated nutrients for repair and support. They can be taken in small amounts based on appetite and used as a meal or snack. Cooked foods, soups, and stews offer foods that are cooked and warm and help replenish digestive energy.
Also, during active treatment many physicians are wary of supplements, and while their prudent use under practitioner guidance is useful, a planned diet can offer combinations of essential nutrients. Since your oncologist will have limited dietary and nutritional background, consultation with a nutritional consultant after treatment can be helpful but will be less productive during treatment as compliance with recommendations can be challenging.
Physical Activity
Physical activity has dual advantages in breast cancer; to reduce the risk of initiation of disease as well as prevent reoccurrence. Using a flexibility program and strength training can each address other aspects of musculoskeletal and vascular conditioning. Higher levels of physical activity above current levels were significantly associated with lower breast cancer risk, but gains toward prevention still occurred at lower levels.
Physical activity was also associated with lower occurrence of breast cancer in postmenopausal women. A study from the National Cancer Institute showed that women doing 2.5-5 hours of moderate intensity/ week or 1.25- 5 hours of aerobic physical activity/week before and for two years after diagnosis had a 55% reduction in recurrence and a 68% reduction in chance of death from any cause. Even with women with family histories of breast cancer or having BRCA genes, regular physical activity reduced all-cause mortality.
One activity that has great potential benefit and could be used both independently and in conjunction with more intense physical activity is Yoga. Studies showed that in those receiving chemotherapy prior to surgery Yoga reduces depression, improves quality of life and allows more women to return to work.
For women undergoing chemotherapy, besides improving overall health and quality of life, yoga improves emotional functioning and decreases fatigue, loss of appetite and constipation.
Obesity and Detoxification
Current beliefs and social norms suggest that obesity is essentially caused by eating too much food. Another perspective might help explain the metabolic reason for weight gain, and why there is such difficulty in losing and maintaining weight loss. There are categories of foods that have higher percentages of environmental toxicants that promote obesity, ill health, and risks for chronic disease. They tend to be highly processed, burdened with preservatives, additives, hidden sugars, and calories and often saturated with pesticides and herbicides. They tend to be many of the convenience foods found in supermarkets and fast-food restaurants.
Our body’s detoxification pathways in the liver and kidney are designed to gather, alter, and remove these undesired chemicals, whether from external sources or our own bodies' growth and repair processes. Our mitochondria also need to detoxify to remain effective. These are the cells that create all our energy through the combustion of sugars, but they also produce byproducts that need removal, to keep our engine running efficiently.
If there are shortages of the necessary universal detoxification resources, priority is given to the liver at the expense of the mitochondria. So, while the mitochondria have plenty of sugar to burn, the engine must gear down till these combustion byproducts are processed. To try to get around this problem the body says, since insulin pushes sugar into the mitochondria let's make more of it.But the system has slowed and can’t use the sugar, so it starts storing it as fat, for a rainy day. As a result, the pounds go on, and if the foods we eat continue to create more toxicants that require more detoxification, the cycle continues, and obesity persists and worsens. If the situation persists for extended periods, we become less sensitive to our own insulin, setting up insulin resistance (IR) and prediabetes. Excess Insulin also produces excess IGF-1, an insulin-like growth factor, that stimulates cellular growth and produces chronic inflammation.
Based on these concepts, a study has shown a 10% greater risk of breast cancer when there is a 10% increase in eating a diet of highly processed foods. Adipose tissue can also be a source of estrogen production as a potential contributor to risk. There is also evidence that weight gain or excess adipose tissue in the postmenopausal time frame raises the risk of developing breast cancer. In women with advanced disease, having insulin resistance (IR) also increases the risk of disease progression.
With the completion of breast cancer and other cancer treatments, detoxification through experienced practitioners can help reduce their toxicity. However, during treatment detoxification should not be considered as it potentially could reduce or increase drug levels causing reduced effectiveness or increased side effects.
Obesity and Breast Cancer Risk
Maintaining a BMI of < 30 is considered an important step in breast cancer prevention. Above this number, premenopausal women are more likely to present with triple-negative and estrogen receptor-negative disease which are associated with a higher risk of invasive disease and mortality.
Adipose tissue can produce estrogen, so with increasing weight comes increased adipose tissue and excess estrogen risk. Also, adipose tissue is a storage depot for many toxins. People who crash diet and lose large amounts of fat also allow large amounts of stored toxic load to be released into our systems. Scientific studies and data are making clear associations between exposures to specific environmental toxins as initiating causes of breast and other cancer.
Current information has shown that, obese women are at greater risk of developing estrogen receptor + breast cancer, and that risk is increased in women with higher BMI than those with a lower BMI. Also, obese women have a worse prognosis over all breast cancer subtypes regardless of menopausal status. Women with higher BMI’s are also at risk for a higher percentage and size of lymph node metastasis. People with high BMI and family history of breast cancer are also at higher risk of breast cancer.
Additional Proactive Recommendations for Navigating Treatments and Reducing Risks
Soy products being included in the diet; in the women who were ER-, ER+PR+ and in both pre and post-menopausal, after breast cancer diagnosis showed improved survival. Please buy soy products that are organic as many commercial products are GMO (genetically modified) and dangerous due to pesticides as well as toxic with arsenic. Its benefits are also shown to improve chemo toxicity, improve quality of life and improve outcomes.
Mushrooms
Coriolus or Trametes improves immune response, increases lymphocytes and natural killer cells.
Dietary mushrooms have an inverse relationship to breast cancer risk; the more you eat the lower the risk (within reason)
Care should be taken with long term continuous use of tricyclic antidepressants and serotonin uptake inhibitors as they can increase the risk of breast cancer. Discuss your concerns with your therapist before changing or stopping these meds.
Vitamin D
There is an Inverse relationship with Vitamin D and breast cancer, the lower the Vitamin D level, the higher risk of breast cancer.
Higher circulating Vitamin D may protect against breast cancer.
Artificial Light in excess at night has a significant correlation with increased risk of breast cancer. Make your sleeping area Dark, and reduce EMR by turning off your phone if close to the bed.
A very recent study reviewed adherence to a Mediterranean diet in breast cancer survivors. They observed that in breast cancer survivors able to follow this diet that there was a positive association with feelings of higher well-being and physical functioning and a diminishing of sleep disorders and pain.
Refrences
Tomlinson-Hansen SE, Khan M, Cassaro S. Breast Ductal Carcinoma in Situ. [Updated 2023 Feb 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567766/
Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007 Oct 4;26(45):6469-87. doi: 10.1038/sj.onc.1210477. Epub 2007 Apr 30. PMID: 17471238; PMCID: PMC3021475.
Application of the Key Characteristics Framework to Identify Potential Breast Carcinogens Using Publicly Available in Vivo, in Vitro, and in Silico Data https://doi.org/10.1289/EHP13233
Holmes DR. Reducing the Risk of Needle Tract Seeding or Tumor Cell Dissemination during Needle Biopsy Procedures. Cancers (Basel). 2024 Jan 11;16(2):317. doi: 10.3390/cancers16020317. PMID: 38254806; PMCID: PMC10814235.
Moo TA, Sanford R, Dang C, Morrow M. Overview of Breast Cancer Therapy. PET Clin. 2018 Jul;13(3):339-354. doi: 10.1016/j.cpet.2018.02.006. PMID: 30100074; PMCID: PMC6092031
Niehoff NM, White AJ, Sandler DP. Physical Activity and Breast Cancer: Focusing on High-Risk Subgroups and Putting Recommendations in Context. Cancer Res. 2020 Jan 1;80(1):23-24. doi: 10.1158/
Goswami S, Adhikary S, Bhattacharya S, Agarwal R, Ganguly A, Nanda S, Rajak P. The alarming link between environmental microplastics and health hazards with special emphasis on cancer. Life Sci. 2024 Oct 15;355:122937. doi: 10.1016/j.lfs.2024.122937. Epub 2024 Aug 3. PMID: 39103046.
Tomlinson-Hansen SE, Khan M, Cassaro S. Breast Ductal Carcinoma in Situ. [Updated 2023 Feb 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2024 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK567766/
Moasser MM. The oncogene HER2: its signaling and transforming functions and its role in human cancer pathogenesis. Oncogene. 2007 Oct 4;26(45):6469-87. doi: 10.1038/sj.onc.1210477. Epub 2007 Apr 30. PMID: 17471238; PMCID: PMC3021475.
Moo TA, Sanford R, Dang C, Morrow M. Overview of Breast Cancer Therapy. PET Clin. 2018 Jul;13(3):339-354. doi: 10.1016/j.cpet.2018.02.006. PMID: 30100074; PMCID: PMC6092031.
Niehoff NM, White AJ, Sandler DP. Physical Activity and Breast Cancer: Focusing on High-Risk Subgroups and Putting Recommendations in Context. Cancer Res. 2020 Jan 1;80(1):23-24. doi: 10.1158
Mnif W, Hassine AI, Bouaziz A, Bartegi A, Thomas O, Roig B. Effect of endocrine disruptor pesticides: a review. Int J Environ Res Public Health. 2011 Jun;8(6):2265-303. doi: 10.3390/ijerph8062265. Epub 2011 Jun 17. PMID: 21776230; PMCID: PMC3138025.
Impact of Plastic-Related Compounds on P-Glycoprotein and Breast Cancer Resistance Protein In Vitro by Matteo Rosellini 1, Petri Turunen 2 and Thomas Efferth 1,*1Department of Pharmaceutical Biology, Institute of Pharmaceutical and Biomedical Sciences, Johannes Gutenberg University, Staudinger Weg 5, 55128 Mainz, Germany and Microscopy Core Facility, Institute of Molecular Biology (IMB), Ackermannweg 4, 55128 Mainz, Germany
*Molecules 2023, 28(6), 2710; https://doi.org/10.3390/molecules28062710
Bloom MS, Clark JM, Pearce JL, Ferguson PL, Newman RB, Roberts JR, Grobman WA, Sciscione AC, Skupski DW, Garcia K, Vena JE, Hunt KJ; ECHO-FGS study group. Impact of Skin Care Products on Phthalates and Phthalate Replacements in Children: the ECHO-FGS. Environ Health Perspect. 2024 Sep;132(9):97001. doi: 10.1289/EHP13937. Epub 2024 Sep 4. PMID: 39230332; PMCID: PMC11373421.
Reproductive endocrine-disrupting effects of triclosan: Population exposure, present evidence and potential mechanisms
Cai-Feng Wang a b, Ying Tian a c https://doi.org/10.1016/j.envpol.2015.07.001
Al-Harthi SE, Alarabi OM, Ramadan WS, Alaama MN, Al-Kreathy HM, Damanhouri ZA, Khan LM, Osman AM. Amelioration of doxorubicin‑induced cardiotoxicity by resveratrol. Mol Med Rep. 2014 Sep;10(3):1455-60. doi: 10.3892/mmr.2014.2384. Epub 2014 Jul 15. PMID: 25059399.
Assessment of herb-drug synergy to combat doxorubicin induced cardiotoxicity. Aditi Jain, Vibha RanDepartment of Biotechnology, Jaypee Institute of Information https://www.sciencedirect.com/journal/life-sciencesTechnology, A-10, Sector-62, Noida 201307, U.P., India
Indole-3-Carbinol and Tamoxifen Cooperate to Arrest the Cell Cycle of MCF-7 Human Breast Cancer Cells1. Carolyn M. Cover; S. Jean Hsieh; Erin J. Cram; Chibo Hong; Jacques E. Riby; Leonard F. Bjeldanes; Gary L. Firestone Cancer Res (1999) 59 (6): 1244–1251.
Martínez-Campa C, González A, Mediavilla MD, Alonso-González C, Alvarez-García V, Sánchez-Barceló EJ, Cos S. Melatonin inhibits aromatase promoter expression by regulating cyclooxygenases expression and activity in breast cancer cells. Br J Cancer. 2009 Nov 3;101(9):1613-9. doi: 10.1038/sj.bjc.6605336. Epub 2009 Sep 22. PMID: 19773750; PMCID: PMC2778514.
Kijima I, Phung S, Hur G, Kwok SL, Chen S. Grape seed extract is an aromatase inhibitor and a suppressor of aromatase expression. Cancer Res. 2006 Jun 1;66(11):5960-7. doi: 10.1158/0008-5472.CAN-06-0053. PMID: 16740737.
Conklin KA. Coenzyme q10 for prevention of anthracycline-induced cardiotoxicity. Integr Cancer Ther. 2005 Jun;4(2):110-30. doi: 10.1177/1534735405276191. PMID: 15911925.
Sayed-Ahmed MM. Role of carnitine in cancer chemotherapy-induced multiple organ toxicity. Saudi Pharm J. 2010 Oct;18(4):195-206. doi: 10.1016/j.jsps.2010.07.008. Epub 2010 Aug 5. PMID: 23960728; PMCID: PMC3730973.