Breast cancer is a disease that takes place when normal breast cells change in a way that their growth becomes out of control. It is predominately a female disease but occurs in men also. It develops from alterations in the functions of genes that normally maintain a balance between cellular growth and the replacement of damaged or senescent cells. There appear to be abnormalities occurring at the genetic level that allows this rapid growth to happen. These genetic changes or mutations can be linked in a small percentage of people to family heredity and are passed from generation to generation. Most causation is still considered to be related to other genetic alterations, but the exact cause of it is unknown.  However, when risks for developing breast cancer are listed many are associated with lifestyle, environmental toxicants and chronic infections and their effects. Other scientists theorize that the origin of these genetic modifications causing cancer are the downstream effect of influences on the gene that trigger changes in the messaging by which genes communicate, initiating this abnormal overexpression of cellular growth. In other words, influences occurring during our lives changes our genetic responses in an adverse way.

Breast Cancer

Overview

Breast cancer develops when there are changes that interfere with normal breast cell growth and repair. Routinely, cellular messages maintain a balance between the removal of damaged and aged cells, and their replacements. It appears that cancer alters this genetic control and creates an environment where uncontrolled rapid growth can occur. While there are hereditary mutations that can be causative, the majority of breast cancer development is unrelated to gene alterations.

The strongest relationships to breast cancer development appear to be associated with poor lifestyle choices, environmental toxicants, and chronic infections. Many studies view these initiating causes as creating messages that do not change gene sequences but rather gene expression or actions, allowing unrestrained cellular control of cell growth.

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. Ductal carcinoma in situ (DCIS), describes the proliferation of cancer cells just within the milk duct without invasion, and will also be diagnosed in 55,000 women. Fortunately, when invasive carcinoma is discovered in its early stages, the survival rate is nearly 100%; but when it has spread 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%.

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 effected, 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

This article will discuss and emphasize the importance of continued surveillance to achieve early diagnosis, risk modification and recognized treatment protocols and preventive strategies.

Statistics reflecting data on treatments and survival are expanding at lightning speed.  The expansion of current knowledge, the new advances in genomics, and the use of contemporary therapies with immune and targeted therapies are expanding and improving treatment options at lightning speed. Along with medical advances, their integration with natural therapies for supportive care is improving and restoring quality of life during and after treatment.

Executive Summary

  • Breast cancer develops when normal cell growth and repair mechanisms are disrupted. While some cases are linked to hereditary mutations, most are not. Environmental factors, lifestyle choices, and chronic infections play significant roles in breast cancer development. The strongest relationships to breast cancer development appear to be associated with poor lifestyle choices, environmental toxicants, and chronic infections.

  • There are several types of breast cancer, each with distinct characteristics. Ductal carcinoma in situ (DCIS) is confined to milk ducts, while invasive ductal and lobular carcinomas can spread to surrounding tissues. Inflammatory breast cancer, though rare, is aggressive and has a poor prognosis. Other types include Paget's disease, papillary breast cancer, and tubular carcinoma, each with unique features and treatment approaches.

  • Breast cancers are often categorized based on their receptor status, which guides treatment decisions. Estrogen receptor (ER) and progesterone receptor (PR) positive cancers can be treated with hormone therapies. HER2-positive cancers respond to targeted therapies like Herceptin. Triple-negative breast cancers, lacking these receptors, are more challenging to treat and often rely on chemotherapy.

  • Risk factors for breast cancer include genetic mutations (like BRCA1 and BRCA2), hormonal factors, and lifestyle choices. Environmental toxins, called endocrine disruptors, can mimic estrogen and potentially increase cancer risk. Obesity, lack of physical activity, alcohol consumption, and exposure to radiation or certain chemicals can also elevate risk.

  • Diagnosis typically involves mammography, which can detect early-stage cancers before they become palpable. Other diagnostic tools include ultrasound, MRI, thermography, and biopsies. Liquid biopsies, a newer technique, can provide real-time molecular profiling of tumors through a simple blood test. Genetic testing may be recommended for those with a strong family history or at high risk.

  • Treatment options vary depending on the type and stage of breast cancer. Surgery (lumpectomy or mastectomy) is often the first line of treatment for localized disease. Radiation therapy may follow to eliminate remaining cancer cells. Systemic treatments like chemotherapy, hormone therapy, and targeted therapies are used based on the cancer's specific characteristics.

  • Targeted therapies are becoming increasingly important in breast cancer treatment. These include hormone therapies like tamoxifen and aromatase inhibitors for ER-positive cancers, and HER2-targeted drugs like Herceptin for HER2-positive cancers. CDK4/6 inhibitors, PI3K inhibitors, and PARP inhibitors are newer targeted therapies showing promise in specific breast cancer subtypes.

  • Breast reconstruction is an option for many women who undergo mastectomy. Options include implant-based reconstruction, autologous tissue reconstruction (using the patient's own tissue), or a combination of both. The timing and type of reconstruction depend on various factors, including the cancer treatment plan and personal preferences.

  • Radiation therapy is often used after breast-conserving surgery or mastectomy to reduce the risk of recurrence. Newer techniques like hypofractionated radiation and partial breast irradiation can reduce treatment time and side effects. Side effects may include skin reactions, fatigue, and in rare cases, heart or lung problems.

  • Chemotherapy can be given before surgery (neoadjuvant) to shrink tumors or after surgery (adjuvant) to eliminate remaining cancer cells. Common side effects include hair loss, nausea, fatigue, and increased risk of infections. Newer targeted delivery methods and supportive care strategies are helping to reduce these side effects.

  • Lifestyle modifications can play a crucial role in both preventing breast cancer and improving outcomes for those diagnosed. A healthy diet rich in fruits, vegetables, and whole grains, regular physical activity, maintaining a healthy weight, and reducing alcohol consumption can all contribute to lower breast cancer risk. Stress reduction techniques like meditation and yoga may also be beneficial.

  • Complementary therapies and natural supplements may help manage side effects of treatment and potentially improve outcomes. These might include acupuncture for pain management, herbal supplements for reducing treatment side effects, or mind-body practices for stress reduction. However, it's crucial to discuss any complementary treatments with your oncologist to ensure they don't interfere with conventional therapies.

  • Ongoing research is exploring new treatment approaches, including immunotherapies, more precise targeted therapies, and strategies to overcome treatment resistance. Clinical trials offer access to cutting-edge treatments and contribute to advancing breast cancer care. Patients should discuss clinical trial options with their oncology team.

  • Survivorship care is an important aspect of breast cancer treatment. This includes regular follow-ups, managing long-term side effects of treatment, screening for recurrence or new cancers, and addressing quality of life issues. Emotional support, through counseling or support groups, can be beneficial throughout the cancer journey.

  • The role of genetics in breast cancer is becoming increasingly understood. Genetic testing can identify individuals at high risk, allowing for more intensive screening or preventive measures. However, genetic testing results can have complex implications and should be accompanied by genetic counseling.

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 based on an inherited germline genetic mutation. The BRCA1 and BRCA2 genes are passed via hereditary and mutations in these genes raise the lifetime risk of breast of breast, 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, in men with these same BRCA1/2 mutations, 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 from ionizing radiation and these mutations also increase breast and ovarian cancer risk. Diagnostic testing for people with specific family backgrounds that could increase risk for these mutations is imperative. There are other less commonly inherited genetic mutations that can result in multiple organ types of cancers in which the breast is one of the target organs in the constellation of disease.

Non-Hereditary Risk Factors

Eighty-five percent of breast cancer cases are unrelated to any family history and occur in later life.  Most oncologists believe that cancer’s origination is from damage to genes that can alter the DNA, which allows uncontrolled growth and proliferation. Because the reasons this happens is unknown, prevention appears difficult.

Other research scientists have shown that DNA damage, from mutations, is not the single cause of breast cancer. Other studies suggest that genes are influenced by chronic foreign pathogens, the effects of specific lifestyle choices, or toxic biochemicals that can affect messages communicated to the gene that changes its actions, rather than altering the gene itself. This then can modify cell growth in an adverse manner potentially creating unwanted replication; Genetic activity is influenced by changing actions not from altering the protein sequences of the gene.

One example would be molecules that mimic the effects of estrogen. The concept, epigenetics, as defined above, implies that these imitators convey information to breast cells that alter estrogen gene expression which stimulates excessive breast cell growth and initiates cancer. Other risk factors that increase estrogen include hormone therapies, liver dysfunction, obesity, and cannabinoids.

These types of epigenetic chemicals are termed Endocrine Disruptors and can be found in pesticides, plasticizers, pharmaceuticals, personal care products and foods and their packaging. They are ubiquitous in the air, groundwater, packing materials and food additives, making them difficult to avoid.

Recognizing and avoiding them is a proactive approach that should be considered along with detoxification strategies for reduction of the body burden. These substances can affect hormone production, its actions, metabolism, and removal from the body. Reduction of these chemicals can be undertaken by trained health practitioners.

  • There are many chemicals that have estrogen activity and can mimic estrogen. They are called xenoestrogens (foreign estrogens), or endocrine disruptors. Examples of pesticides include DDT, DDE, and dioxin. While these have been banned in the US for decades, they still contaminate our groundwater, and the plants and animals that use it.

  • Xenoestrogens are also found in synthetic chemicals like Bisphenol A (BPA) found in plastic disposable water bottles, food wraps, and cash register tapes, and PCBs (polychlorinated biphenyls), and in the mycotoxin Zearalenone.

  • Parabens are endocrine disrupting chemicals that are found in everyday items, being used as a preservative 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; Seventy percent of products contain this ingredient. They also have some estrogenic activity which remains on the skin as parabens inhibit the cell enzymes that would break them down.

There can be difficulty in getting an accurate assessment of the amount in specific products as they are not required to list the amounts on packaging.

For more information, the websites environmental working group and green seal offer help with product labels to reduce exposure. Think Dirty app allows you to scan and see many products as to other possible chemicals you want to avoid.

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. Ninety percent of these early cancers are found on a screening mammogram. The recommendation for screening currently recommends mammography i 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 mammogram. The most common symptoms are a painless firm mass in the subareolar area and imaging is abnormal in 80-90% of cases.

Procedure:

Imaging involves two X-rays of each breast using very low-dose radiation. A screening mammogram 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, 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 (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 instead of 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 breasts also suggest signs of early breast cancer until proven otherwise.

Breast Self-Exam

Liquid Biopsy

The liquid biopsy is a blood test offered currently by several companies. It offers molecular profiling in real time, of circulating tumor DNA, or DNA pieces called nucleic acids, and tumor cells. It is an inexpensive, noninvasive and repeatable test that allows oncologists to assess the response or resistance to specific targeted or chemotherapy and allow changes in therapy if new specific mutations are recognized and might allow enrollment in new clinical trials where therapies for that mutation are being conducted. It also can be used to detect early cancer, and while less likely in breast tumors, can provide vital information if a tumor is inaccessible to biopsy.

Certainly, it is possible that the blood draw might miss the markers sought after, being dependent on the amount of tumor components that are shed into the blood. It is important to appreciate that traditionally, after a tissue biopsy is obtained and therapy has begun, there is no information that can be gained as to its effectiveness except indirectly via imaging or with changing, new or increasing symptoms. This testing therefore offers the possibility of improved treatment protocols and outcomes that can extend longevity.

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, two techniques are used to obtain tissue. One, is a fine needle 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 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 a 85% lifetime risk of breast cancer.

Another choice for obtaining breast tissue is an excisional biopsy which removes the entire mass. It is performed under general anesthesia and requires time in recovery before going home. But regardless of the procedure if cancer is identified then the entire lesion needs removal. As a cost-effective means, insurance prefers needle biopsies, especially since the largest percentage of biopsies are negative. Virtually all hospitals and cancer centers that perform breast biopsies do needle aspirations.

There are a few scattered studies and a few oncology surgeons that believe that when the biopsy needle is being removed, there is a possibility of seeding the needle tract with cancer cells. This opens the possibility that needle aspirations may allow cancer cells to spread to locations like the lymph nodes or via blood to other organs. This possibility has generated interest in the integrative medical community in ways that reduce this potential risk.

A popular recommendation is to use the powdered form of the modified peel and pulp of citrus fruit called modified citrus pectin. There are studies showing that this nutraceutical prevents cancer cells from adhering to blood vessels, increases cancer cell death, and reduces the risk of metastasis. This might be a proactive step to bridge using needle biopsy and possible risks.

Biopsy

Disease Staging:

Staging is a system that tells the physician how far the cancer has spread, and to what location. The international system for disease staging uses the initials, TNM for tumor, 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 the 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.

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.  

Types of Breast Cancer

  • Ductal carcinoma in Situ (DCIS) is the growth of cancer cells inside a milk duct without extension into the tissue around it; representing 20-25% of all breast cancers. Often women with DCIS have radiation or hormonal treatment after lumpectomy. This is often done because the risk of invasiveness with lumpectomy alone is 7.5-13%; but studies have failed to demonstrate that these adjuvant treatments improve long term survival or reduce the rate of metastatic recurrence. Currently, oncotype DCIS tests for 12 genes that can give what is called a recurrence score risk. In women with early-stage breast cancer that is ER+, HER 2- or DCIS this test helps evaluate the threat that the cancer will recur and if this is the case is there a benefit in receiving additional chemotherapy.

  • Lobular carcinoma begins in the cells of the milk producing glands. It is the second most common breast cancer, 5-15%. It is detected 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 while only 1% is the most aggressive and has the poorest prognosis. It blocks breast skin lymphatics and looks red as the breast is 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+.

Subtypes of Breast Cancer Based on Potential Treatment Receptors

Clinical studies and research have also defined precise targeted therapies based on specific cancer cell receptors. If a subtype has a potential receptor there are available treatments to achieve the most efficacious and successful outcomes. These patterns include the following: estrogen (ER), progesterone (PR), epidermal growth factor (HER2), and multiple signaling pathways that kinase, PI3K, and mTOR inhibitors.

Positive hormone receptors occur in approximately three-quarters of breast cancers. These are estrogen-positive (ER+), 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). 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

  • 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 treatment with hormone-blocking drugs

  • Triple Negative Breast Cancers (TNBC) lack the 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 needed for the surveillance of family members.

  • It is most often diagnosed by a clinical examination, often limiting the opportunity and effectiveness of treatment with surgery, radiation, and neo-adjuvant therapies. Because the disease is often more advanced in discovery, relapse is common, and overall survival is markedly decreased compared to other breast cancers that have specific targets for treatment.

The types and subtypes of breast cancer listed provide your oncologist with individual growth characteristics and targeted treatment options.  These decisions are based on large studies looking at receptor status, stage of cancer, genetic testing, and the constitutional or underlying strength of the person. And while there is the scientific data available, there might be multiple therapies that can be utilized. Advocate to participate in your own treatment decisions by requesting information and asking questions and make sure that you connect with your oncologist and feel he or she is strongly supportive of your participation.

Treatment

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 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 1970’s, when clinical trials demonstrated that less extensive surgery was equally effective using the modified radical mastectomy which involved a segmental removal of breast tissue. And 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 the 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.

Reconstruction

There are three types of reconstruction procedures available which are:

  • Devices, 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 from1 and 1000 to 1 and 40,000 people, due to the outer surface material. 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 your 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.

Currently, oncologists are considering treatments that don’t conform to the current standards but are based on their experiences with other patients. Earlier, surgery was THE treatment for breast cancer; however, this perspective is now changing in specific instances. There are instances where chemotherapy or immunotherapy is given, followed by an MRI to evaluate whether the tumor has shrunk or disappeared. While this approach is currently not considered the standard of care, it has proven to be an effective tactic.   

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. And while not curative it may slow disease progression.

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 of the reconstruction or further affect overall healing.

Immediate Reconstruction

Immediate reconstruction can be considered a treatment as well as a prophylactic measure. Surgical techniques are possible that can be used to preserve as much skin as possible and others that can preserve the nipple-areolar area offering the best cosmetic outcomes. This requires coordination between the breast and the plastic surgeon.

Sentinel Nodes

The burden of disease in the axilla is of significance related to ultimate prognosis. Pathological tissue evaluation 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 that can help improve upper arm strength, 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.

Radiation Therapy

In breast cancer, radiation therapy uses high energy particles that break the DNA inside cells and keeps them from dividing and growing, so that they die. Normal cells in the area are also damaged but regenerate over time and grow again. It is a direct treatment that affects a local area which differs from chemotherapy that affects the entire body. It can be used prior to surgery to shrink a tumor or after surgery to help prevent recurrence.

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.

Radiation therapy is designed to fulfill the intention of surgery by destroying any residual tumor. It is intended to reduce the risk of local or regional disease and ultimately improve overall survival. The protocol pertaining to radiation therapy depends on what surgery was performed as well as the extent of the disease.

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.

Women who have had a mastectomy often have a greater burden of disease. Cells may remain in the chest wall or lymph nodes, so radiation is an option. Treatment with radiation is considered in the following situations: nodal involvement, indicating spread beyond the breast, for larger tumors and in situations where after the tumor is removed the margins still test positive for cancer. Radiation is still used, and helpful for advanced diseases to reduce symptoms of pain.  Treatments have historically been 5 days a week for 5-6 weeks. Currently, some centers will do whole breast irradiation 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 ensure the high 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. Consult with 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. Topical creams such as calendula, 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. If 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.

Targeted Therapies for Breast Cancers

Pharmaceuticals Therapies

Hormonal, or Endocrine Therapies

There is a direct connection between estrogen and the development of breast cancer. Breast cells have estrogen receptors that when stimulated by excessive estrogens can increase growth or proliferation and lead to cancer, and in a person with breast cancer, estrogen will accelerate it.

These drug therapies affect the estrogen cancer cell receptors and take away its ability to continue estrogen-mediated cell growth. Treatment with estrogen blocking drugs also have ill effects. They are called side effects but are other affects you get when you use estrogen blocking treatment.

This aspect of cancer drug treatment, the ill or side effects, extends to involve cancer treatments; there is a risk-benefit situation with the expectation that the treatment, despite its side effects, will be beneficial to controlling the disease.

These drug therapies include the following:

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 treatment.

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.

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 an individual’s survival. 

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 were the same for risk of heart attack or stroke.

  • EGCG enhances the effectiveness of tamoxifen.

  • It is also necessary to avoid Curcumin and DIM(Diindolylmethane) as they can reduce the effectiveness of tamoxifen.

  • Menopausal symptoms can be extremely bothersome and can be successfully addressed by practitioners of Chinese medicine.

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 still can produce estrogen. So, to diminish this production, these drugs block conversion to estrogen.

The following supplements have been shown when tested on living breast cancer cells, not patients, to potentially offer value in treatment.

  • Studies using breast cancer cells demonstrate Melatonin decreases aromatase activity both by regulating gene areas that promote its production and its anti-estrogen effect, thereby supporting Aromatase inhibitor drugs.

  • Grape Seed Extract also is 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 it degrades 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 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.

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 resistant to it over time. The addition of these drugs can enhance hormone therapies also, but with increased side effects.

Kinase Inhibitors for HR+ Disease

Adjuvant CDK 4/6 or Cyclin-Dependent Kinase Inhibitors in HR+ disease:

Ibrance (Palocicib), Verzenio (Abemacicib) Kisquali (Ribcicib), are kinase inhibitors, kinase inhibitors can often be recognized with their (ib) suffix.

CDK or inhibitors target the communication within the cell’s 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 nodes and are 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 81%, red cells 83%, platlets 60%

  • 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 especially 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 with advanced disease. It also may stop the tumor from developing new blood vessels.

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 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.

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 2 chemotherapies. 

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:

Side effects include:

  • 52%, severe skin reaction

  • 85%, diarrhea 85%,

  • 79%, elevated glucose

Antibody-Drug Conjugate

Side effects:

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.

Human Epidermal Growth Factor

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. 

  • Quercetin down regulates both HER 2 and PI3K which is the pathway which signals HER 2 overexpression.

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.

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 Herceptin

  • 47%, pain

  • 36%, chills and fever

  • 22%, abdominal or back pain

  • 25%, vomiting or diarrhea

  • 26%, cough

  • 18%, rash

Antibody-Drug Conjugates (ADC)

Other Serious Side Effects of HER-2 Drugs

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 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.

This is also an oral drug that is given for one year after a person has been treated, for early-stage breast cancer, using trastuzumab. It is also indicated in metastatic disease along with capecitabine but usually after other HER 2 targeted drugs have been tried.

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 (Fam-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.

Kinase Inhibitors for HER 2 +Therapies Targeted Therapies

Side effects:

Side effects of Lapatinib include:

  • 44%, Diarrhea, and nausea

  • 44%, Rash

  • 45%, Elevated liver tests

  • 56%, Low hemoglobin

Nerlynx (Neratinib)

Side effects:

Side effects of Neratinib include:

  • 65%, Diarrhea

  • 45%, Elevated liver tests

  • 44%,Rash

  • 56%,Low hemoglobin

Tukysa (Tucatinib)

Side effects:

Side effects of Tucatinib include:

  • 95%, Diarrhea

  • 53%, Nausea

  • 63%, Hand & Foot syndrome rash

  • 35%, Loss of appetite

Targeted Therapy in 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

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.

Talzenna (Talazoparib) 

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 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)

Triple negative breast cancer, TNBC, is a subtype that is lacking in estrogen, progesterone or HER-2 receptors and so is not sensitive to hormone or HER 2 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.

Trodelvy (Sacituzumab govitecan) is another example of a monoclonal antibody but combined together with a chemotherapy drug for used 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. 

Antibody Drug Conjugate

Side effects:

Side effects of Trodelvy include:

  • 84%, low neutrophils and lymphocytes counts.

  • 69%, decreased red blood cell counts.

  • 69%, diarrhea

Common Theraputic Protocols 

Preparation for Cytotoxic Chemotherapy

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 blood stream 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 hormone or targeted therapies.

If the risk of recurrence is low consideration should be given as to its risk vs. its benefit. If the risk is small but the possibility of serious side effects is significant, it might outweigh its benefit. When the expected length of survival is a goal, discussing considerations such as advanced age or significant other diseases needs to be weighed in deciding the benefit vs the risk of side effects in continuing or changing.

In addition, as with virtually all cancer pharmaceuticals, cytotoxic drugs prevent the growth or production of cells that are rapidly growing; both normal and abnormal, and while the goal is to destroy cancer cells, our other rapidly recycled non-cancerous cells are affected; blood cells, hair, and cells from the GI system suffer during the treatment.

Prior to the infusion, given at the oncologists, a pre administration evaluation is needed each time to assure 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. And 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 can be given a few days after treatment if needed.

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 (ILGF-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.

  • Summarizing recent studies reveals the following: studies showed that 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 lower occurrence of breast cancer in postmenopausal women. A study from the National Cancer institute showed that in 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 reoccurrence 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, 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 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 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.