Treatment & Management of Breast Cancer

Understand the role of surgery, radiation, hormonal and chemotherapy for the treatment of breast cancer.

Treatment & Management of Breast Cancer

Medically reviewed by Dr. C.H. Weaver M.D. Medical Editor 8/2018

In general treatment for breast cancer may require surgery, radiation, and/or systemic therapy with chemotherapy, immunotherapy or precision cancer medicines. The specific treatment for each person is individualized and is based on the stage of the cancer and its genomic profile.

Surgery for Breast Cancer

Nearly all women with breast cancer will undergo some kind of surgery as part of their diagnosis and/or treatment. The extent of surgery for breast cancer may range from removal of only a small piece of breast tissue to removing one or both breasts, including underarm (axillary) lymph nodes. In addition to treating the cancer, the purpose of surgery in the management of breast cancer is to obtain tissue to confirm an accurate diagnosis, determine the stage of the cancer, and provide for breast reconstruction to create a breast that matches the opposite breast.

Surgical Treatment for Breast Cancer, Learn More...

Systemic Treatment for Breast Cancer

Systemic cancer treatment is administered to decrease the risk of cancer recurrence that occurs following treatment with surgery alone for most patients with early stage breast cancer. Systemic treatment may be given before (neoadjuvant) or after (adjuvant) surgery and may include chemotherapy, hormonal therapy, immunotherapy, or use of precision cancer medicines. Neoadjuvant therapy is typically used in individuals with “larger” cancers to shrink them before surgery in order to obtain a complete removal by surgery. Systemic therapy is the standard treatment with for all advanced breast cancers.

Precision Cancer Medicines

The purpose of precision cancer medicine is to define the genomic alterations in the cancers DNA that are driving that specific cancer. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed. Precision medicines are being developed for the treatment of colon cancer and patients should ask their doctor about whether testing is appropriate.

Precision Cancer Medicines for the Treatment for Breast Cancer, Learn More...

Chemotherapy

Chemotherapy uses medications that can be taken orally as a pill or are injected into a vein to kill cancer cells. In some situations chemotherapy is combined with immunotherapy or other precision cancer medicines to achieve the best results.

Hormonal Therapy

Estrogen is an essential female hormone that is produced by the ovaries and adrenal glands. Estrogen can cause some cancers to grow. The breasts, uterus and other female organs are composed of cells that contain estrogen receptors. When cells that have estrogen receptors become cancerous, exposure to estrogen increases the cancer’s growth. Cancer cells that have estrogen receptors are referred to as estrogen receptor-positive (ER-positive) cancers.The growth of ER-positive breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. This is the goal of hormonal therapy for breast cancer.

Hormonal Treatment for Breast Cancer, Learn More...

Radiation

Radiation therapy uses high-powered energy beams, such as X-rays or protons, to kill cancer cells. Radiation therapy is almost always utilized as part of the overall breast-conserving strategy in early stage cancer and DCIS because radiation decreases the risk of local cancer recurrence and improves survival.

Radiation Treatment for Breast Cancer, Learn More...

Treatment of Breast Cancer by Stage

Stages

Carcinoma In Situ: Approximately 15-20% of breast cancers are very early in their development. These are sometimes referred to as carcinoma in situ and consist of two types: ductal carcinoma in situ (DCIS), which originates in the ducts and lobular carcinoma in situ (LCIS), which originates in the lobules. DCIS is the precursor to invasive cancer and LCIS is a risk factor for developing cancer.

Stage I: Cancer is confined to a single site in the breast, is less than 2 centimeters (3/4 inch) in size and has not spread outside the breast.

Stage IIA: Cancer has spread to involve underarm lymph nodes and is less than 2 centimeters (3/4 inch) in size or the primary cancer itself is 2-5 centimeters (3/4-2 inches) and has not spread to the lymph nodes

Stage IIB: Cancer has spread to involve underarm lymph nodes and/or the primary cancer is greater than 5 centimeters (2 inches) in size and does not involve any lymph nodes.

Stage IIIA: Cancer is smaller than 5 centimeters (2 inches) and has spread to the lymph nodes under the arm or the lymph nodes are attached to each other or to other structures or the primary cancer is larger than 5 centimeters (2 inches) and has spread to the lymph nodes under the arm.

Stage IIIB: Cancer directly involves the chest wall or has spread to internal lymph nodes on the same side of the chest.

Inflammatory: Inflammatory breast cancer is a special class of breast cancer that is rare. The breast looks as if it is inflamed because of its red appearance and warmth. The skin may show signs of ridges and wheals or it may have a pitted appearance. Inflammatory breast cancer tends to spread quickly.

Stage IV: Cancer has spread to distant locations in the body, which may include the liver, lungs, bones or other sites.

Recurrent/Relapsed: The breast cancer has progressed or returned (recurred/relapsed) following an initial treatment.

Surgery For Breast Cancer

Nearly all women with breast cancer will undergo some kind of surgery as part of their diagnosis and/or treatment. The extent of surgery for breast cancer may range from removal of only a small piece of breast tissue to removing one or both breasts, including underarm (axillary) lymph nodes. The purpose of surgery in the management of breast cancer is to:

  • Obtain a tissue sample for determining an accurate diagnosis.
  • Evaluate the tissue to determine if precision cancer medicines can be used to treat the cancer
  • Determine the stage of the cancer and whether additional treatment is necessary.
  • Treat the cancer locally.

The surgical procedures utilized in the management of breast cancer include the following. The type of surgery that a patient with breast cancer undergoes depends largely on the size and location of the cancer, the breast size, feasibility of breast reconstruction, and how important breast preservation is to the patient.

Biopsy

A biopsy is the removal of cells or tissue for further evaluation; it is often performed to determine whether cancer is present. A biopsy may involve surgical removal of all or a part of a breast lump, or use of a needle to remove tissue or fluid.

Mastectomy

A simple (total) mastectomy involves the removal of the entire breast, but not the axillary (underarm) lymph nodes.

There are also different degrees of mastectomy, including the following:

  • Partial (segmental) mastectomy is the removal of one-quarter or more of the breast and the lining over the chest wall. This may include removal of axillary lymph nodes. Reconstruction may be difficult after a partial mastectomy because of the drastic change to the contour and size of the breast after the procedure.
  • Radical mastectomy is an aggressive therapy that consists of extensive removal of the entire breast, the lymph nodes under the arm in the axilla and the chest wall muscles under the breast.
  • Modified radical mastectomy involves the removal of the entire breast and the lymph nodes in the axilla under the arm.

Lumpectomy

Removal of the cancer and a portion of surrounding tissue is called a lumpectomy. Because a lumpectomy alone is associated with a higher rate of cancer recurrence than mastectomy, patients who elect to have a lumpectomy are also treated with radiation therapy. This combination of lumpectomy and radiation therapy is called breast-conserving therapy. Among women with early-stage breast cancer, breast-conserving therapy and mastectomy produce similar rates of long-term survival.[1]

Axillary Lymph Node Evaluation

Evaluation of early stage breast cancer typically includes a biopsy and removal of axillary (under arm) lymph nodes in order to help determine the stage of the cancer and whether the cancer has spread outside the breast. This is important because when axillary lymph nodes have cancer, more aggressive treatment is required in order to achieve the best chance for cure.

For over 30 years, the standard of practice for evaluating lymph nodes has been a surgical procedure called an axillary lymph node dissection. This procedure involves the removal of approximately 10-25 axillary lymph nodes and may be performed during the initial surgery or as a separate procedure.

Although the performance of an axillary lymph node dissection has helped doctors and patients determine optimal treatment, removal of the axillary lymph nodes is commonly associated with chronic side effects. In addition to the risk of infection and other local complications of surgery, an axillary lymph node dissection can result in lymphedema, which is a buildup of lymph fluid in the tissues just under the skin. As blood circulates through the body and travels into smaller and smaller vessels, excess fluid, protein and other substances are pushed out into the surrounding tissue. This substance is called lymph fluid. Under normal circumstances, lymph fluid is removed from the tissues by the lymph system, which is a series of vessels and organs that moves the fluid back toward the heart and filters it through lymph nodes. Lymph nodes are specialized structures that are composed of white blood cells and serve to “clean” the lymph fluid of bacteria or other contaminants. When lymph nodes are removed, the lymph fluid builds up in the tissues. This build up of fluid may result in chronic swelling, numbness, limited shoulder motion, and pain to the arm on the side of the body that the surgery was performed.

Doctors have long desired a way to evaluate axillary lymph nodes that would result in less discomfort for patients. A sentinel lymph node biopsy is one way to accurately evaluate axillary lymph nodes and is associated with fewer side effects than axillary lymph node dissection.

Sentinel lymph node biopsy: A newer approach to evaluating axillary lymph nodes for spread of cancer is called a sentinel lymph node biopsy. This procedure involves removing a single lymph node (or a small number of nodes), called the sentinel node, which is the first lymph node to collect excess fluid surrounding the cancer. Prior to surgery, blue dye is injected near the cancer. The dye drains from the area containing the cancer into the nearby lymph nodes, through the sentinel node. The node containing the dye is removed during surgery and evaluated under a microscope to determine whether cancer has spread. If the sentinel node is free of cancer, more extensive lymph node surgery is usually not required.

Sentinel lymph node biopsy is becoming the standard approach for determining whether cancer has spread to the axillary lymph nodes.[2] The procedure appears to be just as effective in determining cancer spread to axillary lymph nodes as an axillary lymph node dissection, and results in fewer side effects.[3]

Breast Reconstruction

Breast reconstruction surgery has become increasingly refined and can be successfully accomplished in almost all women treated with mastectomy. The goal of breast reconstruction surgery is to create a breast that matches the opposite breast. This can be accomplished by using a breast implant alone, by actually reconstructing the breast with the patient’s own tissue, or by utilizing a combination of these two techniques. Breast reconstructive surgery can be performed immediately after mastectomy or it can be delayed for some time. If chemotherapy treatment or if radiation is to be given to the chest wall, many doctors prefer delayed reconstruction so that the healing of the reconstructed breast is not impaired.

The two techniques commonly used in breast reconstruction are:

  • Synthetic breast implants
  • Autologous reconstruction, which utilizes the patient’s own tissue

It is recommended that patient include a plastic surgeon in their team of physicians as early in their treatment as possible so that their chosen method of breast reconstruction can be incorporated into the overall treatment plan.

Breast implants: The simplest method of reconstructing the breast is with the use of synthetic implants. During this procedure, an implant that closely approximates the size and shape of the other breast is inserted through the mastectomy incision, under the pectoralis major (chest muscle). Implant surgery is relatively simple and can be performed at the time of initial surgery or delayed until after all treatment is completed. If performed at the time of mastectomy, implant surgery adds an additional 30 minutes or approximately 1½ hours is required if it is delayed and performed as a separate surgical procedure. Recovery from implant surgery is typically quicker after immediate reconstruction than after delayed reconstruction.

The procedure of implant surgery usually requires the surgeon to insert a temporary tissue expander under the pectoralis muscle in order to stretch the muscle and the skin over the chest wall. The tissue expander contains a valve-like opening or port through which small amounts of saline (salt water) can be injected. Every week or two, saline is injected into the expander until it is inflated to a size slightly larger than the implant. Because the expansion occurs gradually, there is minimal pain or discomfort associated with the procedure. When the tissue has been expanded to the point where it can accommodate the breast implant, the expander is replaced with the permanent implant.

If there is not enough skin to cover the implant, the muscle over the chest wall has been removed, or the skin has been damaged by radiation and cannot be stretched, the surgeon can remove a fan-shaped section of muscle and skin from the back that remains attached to a portion of skin or pedicle. The pedicle contains the blood supply for the flap and this procedure is referred to as the latissimus dorsi flap. The flap is tunneled under the skin and pulled out through an opening in the chest where it is sutured in place over the mastectomy site. The implant can then be placed under the muscle to complete the reconstruction. The latissimus dorsi flap procedure is more complicated than a simple implant insertion. It leaves a scar on the woman’s back and requires a longer recuperation. There is a potential for shoulder problems because a portion of the muscle required for shoulder motion has been removed. However, this procedure usually creates a better result than an implant, especially in women with large breasts or those who have received previous radiation treatment. The risks and benefits of the various implant procedures should be carefully discussed with your surgeon in order to achieve the best results.

There are currently two types of implants available in the United States for breast reconstruction, silicone gel implants and saline-filled implants.

Silicone gel implants have generated a fair amount of controversy regarding their safety because of the question as to whether they can trigger certain connective tissue and autoimmune diseases. In 1992, the Food and Drug Administration restricted the use of silicone implants in order to evaluate whether they were indeed associated with autoimmune conditions. Patients who desired reconstructive surgery with silicone gel implants after mastectomy were given access to clinical trials. Studies completed thus far have failed to show an increased risk of autoimmune disease among women with silicone implants, although the follow-up is relatively short. It is interesting to note that other countries did not take silicone implants off the market.

Saline-filled implants have not been associated with any risks. If saline implants leak, the saline is absorbed into the body and is harmless. Many women prefer the silicone gel implants to the saline filled implants because the silicone feels more like breast tissue.

Autologous reconstruction of the breast: Autologous reconstruction of the breast utilizes the body’s own tissue to build a mound that feels and appears like a natural breast. Autologous breast reconstruction is major surgery compared to breast implants. It requires several hours in the operating room and is associated with the complications of any major surgery. Two major surgical techniques are currently used for autologous reconstruction of the breast. These are the TRAM flap (transverse rectus abdominis myocutaneous) and the free flap.

The TRAM flap procedure utilizes tissue taken from the woman’s abdomen. Tissue containing a section of the skin, the underlying fat, and a portion of the abdominal muscle is excised except for one or two pedicles of tissue, which remain attached to the abdomen. The remaining attached tissue serves as the blood supply for the flap that will be used to reconstruct the new breast. The flap is tunneled under the abdominal wall to the chest and then rotated to fit the mastectomy wound. The smooth edges are made by attaching the edges of the breast incision to the flap. The TRAM flap procedure thus creates a breast with a natural texture very similar to a normal breast. Side effects associated with the TRAM flap procedure may include abdominal weakness and an increased risk of developing an abdominal hernia, which is a bulging of the internal tissues through an area of weakness in the abdominal wall. Because of these potential problems, modifications of the TRAM flap technique have been developed. These newer techniques limit the amount of muscle which is removed with the flap.

A free flap, or a free TRAM, utilizes an island of fat and skin that is entirely removed from the abdomen. Since the fat and skin are completely excised from the abdomen, a new blood supply to the tissue must be provided. This requires a surgeon who specializes in microsurgery to attach the blood vessel supply in the flap to those in the chest wall. This procedure is technically more difficult to perform than the TRAM flap, but less muscle is removed. An even more complicated technique called a Deep Inferior Epigastric Perforator (DIEP) flap removes no muscle.

Reconstructive surgery utilizing breast implants, autologous reconstruction of the breast, and other new surgical techniques will continue to be developed and refined in order to produce the best breast reconstruction for women desiring this procedure. Each of the currently available techniques has advantages and disadvantages that will be unique to each patient’s circumstance. Individuals deciding to undergo breast reconstruction surgery should discuss these options with a qualified plastic surgeon in order to ensure the result they achieve is satisfactory.

**Skin-sparing mastectomy:**A new mastectomy procedure is being developed at several surgical oncology programs around the United States. A skin-sparing mastectomy removes the entire breast tissue, similar to a mastectomy, but leaves the skin covering the breast intact and capable of housing fat and muscle from other parts of the body. The procedure is more difficult than a traditional mastectomy in that the surgeon must make a small incision in the breast about the size of a half-dollar and then carefully remove all the breast tissue inside the breast. When done correctly, an empty envelope of skin exists that can than be filled with fat and muscle taken from the woman’s back or abdomen. Because the surgery uses fat from the woman’s own body, the newly constructed breast behaves just like the companion breast when weight is gained or lost.

Radiation Therapy For Breast Cancer

The objective of radiation therapy to the breast is to kill cancer cells that could otherwise persist after therapy and cause breast cancer to relapse locally in the breast, surrounding chest wall, or axilla. Radiation therapy uses high energy x-rays to kill cancer cells that remain in the breast or surrounding lymph nodes after surgery. Radiation therapy is almost always utilized as part of the overall breast-conserving strategy because radiation decreases the risk of local cancer recurrence and improves survival. Radiation therapy is often delivered to the breast and surrounding lymph nodes from a machine outside the body and is called external beam radiation therapy. Treatments are typically given daily over a 5-6 week period and additional concentrated radiation treatment, called a boost, may be given directly to a smaller area of the breast where the cancer was found.

Side effects from external radiation therapy may include a swelling or heaviness in the breast, sunburn-like changes in the skin, and fatigue. Changes to the breast and skin usually go away in 6-12 months; however, in some women the breast may become smaller or firmer following radiation therapy. The size of the breast and the woman’s desire for breast reconstructive surgery are important considerations that should be addressed prior to receiving radiation treatment.

Breast brachytherapy is an alternative to traditional external beam radiation therapy for women who choose breast-conserving surgery. With breast brachytherapy, a site-specific, prescribed dose of radiation is administered during a five-day course of therapy. Because of the relatively short duration of the treatment course, breast brachytherapy is an attractive option for women who choose lumpectomy over mastectomy, but do not wish to undergo six weeks of external beam radiation therapy. Women should discuss with their doctor, however, whether this is an appropriate approach for them.

The procedure for breast brachytherapy involves inserting a deflated balloon into the cavity where the tumor was removed. An applicator shaft, or catheter, connects the balloon to the outside of the breast. The balloon is filled with saline, and both the balloon and the catheter remain in place during the time the woman is undergoing treatment. The radiation therapy is performed on an outpatient basis in a five-day-long, twice-per-day sequence of treatments. During the treatment, a radioactive “seed” is inserted into the catheter within the balloon in an exact dose, minimizing radiation exposure to the rest of the breast, skin, ribs, lungs, and heart. No source of radiation remains in the patient’s body between treatments or after the final procedure. The catheter and balloon are removed after the final procedure.

Ductal Carcinoma In Situ (DCIS)

Patients with DCIS treated with mastectomy do not need treatment with radiation therapy. Radiation therapy after a lumpectomy decreases the risk of cancer recurrence. In one clinical study, 818 women with DCIS and negative surgical margins were treated with breast radiation or no further therapy after a lumpectomy. Eight years following treatment, the recurrence of invasive cancer was 3.9% for patients treated with radiation therapy and 13.4% for patients not treated with radiation therapy.

Stage I Breast Cancer

Patients with node-negative Stage I breast cancers treated with breast-conserving surgery utilizing a lumpectomy are currently recommended to receive additional treatment with radiation therapy. This recommendation is based on several clinical studies that directly compared lumpectomy to lumpectomy plus radiation treatment. These studies found that patients treated with the combination of lumpectomy plus radiation had a superior clinical outcome. Other clinical studies have demonstrated that patients treated with lumpectomy without radiation are more likely to experience cancer recurrence than women treated with the combination of breast-conserving surgery and radiation.

Standard radiation therapy following a lumpectomy consists of a limited dose of radiation (50 Gy) to the entire affected breast. While this treatment leads to long-term outcomes similar to those from mastectomy, women under age 50 experience higher rates of local recurrences following this treatment regimen compared to their elder counterparts. Researchers have theorized that an additional boost of radiation aimed only at the area from which the cancer was removed would reduce the rates of local recurrences, especially in younger patients.

The European Organization for Research and Treatment of Cancer conducted a clinical trial evaluating 5,318 women diagnosed with Stage I or II breast cancer who had undergone a lumpectomy followed by the standard dose of radiation. Approximately half of the patients were given an additional small dose of radiation (16 Gy) to the area where the cancer had been located, while the other half received no additional treatment. Data indicated that the additional dose of radiation to the site of the removed cancer reduced the overall rate of a local recurrence by nearly 50%. Women 40 years old and younger exhibited the largest benefit, with local recurrences occurring in only 10.2% of patients receiving additional radiation, compared to 19.5% of those receiving standard treatment. Overall survival rates and the development of distant metastases were similar whether women received an additional boost of radiation or standard therapy. Side effects including cosmetic results and fibrosis (formation of scar tissue) were not affected by the additional radiation.

Patients with Stage I node-negative breast cancers treated with mastectomy generally do not require additional local treatment with radiation therapy. Some patients treated with mastectomy may however have an increased risk of local cancer recurrence. In these cases, the role of radiation therapy to prevent local cancer recurrence should be discussed with the treating oncologist. Node-negative cancers at increased risk of local recurrence include cancers that involve the margin of resection.

Stage II-III Breast Cancer

Patients with node-negative Stage II breast cancers treated with breast-conserving surgery utilizing a lumpectomy are currently recommended to receive additional treatment with radiation therapy because radiation decreases the risk of local cancer recurrence and improves survival.

The role of radiation therapy following mastectomy in women with Stage II or III breast cancer is somewhat controversial. An analysis of several clinical studies begun before 1985 found that radiation decreased the risk of local cancer recurrence by 67% and decreased the risk of dying from breast cancer by 6%, but did not improve survival. Survival was not improved because patients treated with radiation died for other reasons. These deaths resulted mainly from heart problems in older patients and could have been a late side effect from the radiation treatment. Because of these analyses, radiation therapy was not typically recommended for women with Stage II or III breast cancer treated with mastectomy.

Standard radiation therapy following a lumpectomy consists of a limited dose of radiation (50 Gy) to the entire affected breast. While this treatment leads to long-term outcomes similar to those from mastectomy, women under age 50 experience higher rates of local recurrences following this treatment regimen compared to their elder counterparts. Researchers have theorized that an additional boost of radiation aimed only at the area from which the cancer was removed would reduce the rates of local recurrences, especially in younger patients.

The European Organization for Research and Treatment of Cancer conducted a clinical trial evaluating 5,318 women diagnosed with Stage I or II breast cancer who had undergone a lumpectomy followed by the standard dose of radiation. Approximately half of the patients were given an additional small dose of radiation (16 Gy) to the area where the cancer had been located, while the other half received no additional treatment. Data indicated that the additional dose of radiation to the site of the removed cancer reduced the overall rate of a local recurrence by nearly 50%. Women 40 years old and younger exhibited the largest benefit, with local recurrences occurring in only 10.2% of patients receiving additional radiation, compared to 19.5% of those receiving standard treatment. Overall survival rates and the development of distant metastases were similar whether women received an additional boost of radiation or standard therapy. Side effects including cosmetic results and fibrosis (formation of scar tissue) were not affected by the additional radiation.

In late 1997, the results of two clinical studies evaluating treatment with mastectomy followed by chemotherapy with or without radiation in premenopausal women with Stage II-III breast cancer were reported in the New England Journal of Medicine. In both studies, women treated with radiation following mastectomy and chemotherapy lived longer and were less likely to develop a recurrence of cancer. Radiation therapy decreased the risk of dying from cancer by approximately 33%. The probability of surviving 10 years from treatment was increased from 54% to 64% and 45% to 54% in the two studies, respectively. No significant long-term side effects of radiation therapy were reported. Current evidence increasingly supports the use of radiation following surgery and chemotherapy in women with Stage II or III breast cancer. Certain groups of women known to be at high risk of local breast cancer recurrence should strongly consider radiation therapy. These include:

  • Cancer greater than 5 centimeters in greatest dimension
  • 4 or more involved axillary lymph nodes
  • Cancer involving the margin of resection

What is the Optimal Sequence of Radiation in Stage I-III Breast Cancer?

The timing or sequence of radiation therapy may be important. A large clinical study has addressed the question of whether radiation therapy should be given before or after chemotherapy following breast-conserving surgery. Following breast-conserving surgery, half the patients were treated with chemotherapy followed by radiation and half were treated with radiation followed by chemotherapy. The patients treated with chemotherapy followed by radiation were more likely to be alive 5 years from treatment than patients treated with radiation followed by chemotherapy. Patients treated with chemotherapy survived longer because they were less likely to experience systemic (metastatic) recurrence of their cancer. Patients treated with radiation first, however, were less likely to experience a local recurrence of their cancer.

It is much easier to treat local recurrence of cancer than systemic recurrence of cancer and this may explain why patients treated with chemotherapy followed by radiation had improved survival compared to patients treated with radiation followed by chemotherapy. An additional explanation is that delivering radiation therapy before chemotherapy treatment of systemic disease may adversely affect the doctor’s ability to deliver the chemotherapy treatment. Although the sequence of treatments is undergoing continued evaluation, the current data suggest that standard treatment of breast cancer outside the context of a clinical study should include definitive surgery first, followed by systemic chemotherapy and lastly, radiation. Hormone therapy can begin during or following radiation therapy. One notable exception to this sequence is patients with locally advanced breast cancer. In these patients, administration of chemotherapy prior to surgery (neoadjuvant) may allow for greater breast conservation.

Stage IV or Recurrent Breast Cancer

Radiation therapy also plays an important role in women with Stage IV or recurrent breast cancer. Chemotherapy and hormonal treatment are the mainstay for women who have Stage IV breast cancer at the time of diagnosis. Local control of breast cancer eradication has less impact on a patient’s outcome because the major cause of treatment failure is systemic cancer recurrence. Therefore, radiation therapy to the involved breast has not typically been recommended for women receiving systemic chemo-hormonal therapy for metastatic breast cancer.

More recent aggressive chemotherapy treatment of Stage IV breast cancer has been reported to produce long-term survival without cancer recurrence in 15-20% of women. Since these women are not experiencing a systemic cancer recurrence, prevention of cancer recurrence in the breast or lymph nodes is of greater importance. The results of a clinical study in which women with Stage IV breast cancer achieving a complete remission to chemotherapy followed by high-dose chemotherapy and autologous stem cell transplant and local radiation to the breast was recently reported and raises the question of whether radiation may be beneficial in women with Stage IV breast cancer in complete remission.

In this study, the patients in complete remission treated with radiation therapy had a lower relapse rate and were more likely to be alive without evidence of cancer recurrence than women not treated with radiation therapy. The chance of relapse was 36% in patients not treated with radiation, compared to 19% in patients treated with radiation. Thirty-one percent of patients treated with radiation were alive without evidence of cancer recurrence at 4 years following treatment, compared to 21% of patients who were not treated with radiation. Patients treated with radiation were also more likely to live longer, with 30% alive 4 years following treatment, compared to only 16% of patients not treated with radiation.

While this clinical study was not designed to evaluate the role of radiation therapy in patients achieving a complete remission to chemotherapy, consolidative treatment with radiation therapy after chemotherapy-induced clinical remissions in women with Stage IV breast cancer appears to reduce the risk of cancer recurrence and may improve a patient’s chance of overall survival. Future clinical studies will need to be designed to evaluate the role of radiation in patients with Stage IV breast cancer in a more formal manner.

Radiation for Palliation

Radiation therapy also plays an important role in providing symptomatic relief from advanced breast cancer. Patients developing metastatic cancer to the bone, skin, selected lymph nodes, and other sites can achieve a complete remission when treated with radiation to the site of cancer recurrence. Radiation can relieve symptoms from cancer and prevent fractures of bones when used early.

Hormonal Therapy for Breast Cancer

Estrogen is an essential female hormone that is produced by the ovaries and adrenal glands. It serves many critical functions in the body, including developing the female sex organs in puberty, preparing the breasts and uterus for pregnancy in adulthood, and maintaining cardiovascular and bone health. Without estrogen, the female body is unable to sustain pregnancy and is susceptible to heart disease and osteoporosis.

Estrogen can also cause some cancers to grow. The breasts, uterus and other female organs are composed of cells that contain estrogen receptors. When cells that have estrogen receptors become cancerous, exposure to estrogen increases the cancer’s growth. Cancer cells that have estrogen receptors are referred to as estrogen receptor-positive (ER+ positive) cancers.

The growth of ER+positive breast cancer cells can be prevented or slowed by reducing the exposure to estrogen. This is the goal of hormonal therapy for breast cancer. However, a reduction in estrogen levels can also result in side effects because estrogen is necessary for important body functions, such as bone growth and cardiovascular health. Lower estrogen levels lead to decreased bone density and heart disease.

Tamoxifen is an anti-estrogen drug that has historically been a mainstay of hormonal therapy. Tamoxifen has largely been replace by aromatase inhibitors (AI) and Faslodex (fulvestrant), alone or combined with cyclin-dependent kinases (CDK) inhibitors because they are better at delaying cancer progression and prolonging survival.

How Does Hormonal Therapy Work?

In premenopausal women, the ovaries are the major source of estrogen. After menopause, when ovarian hormone production drops dramatically, some estrogen continues to be produced in tissues outside of the ovaries. In this process, androgens produced by the adrenal glands are converted into estrogen. An enzyme called aromatase is required for this conversion.[1]

The goal of hormonal therapy is to decrease the effect of estrogen on cancer cells. Reducing the effects of estrogen can be accomplished in the following ways:

  • by removing the ovaries, which produce the majority of estrogen in premenopausal women
  • by blocking the conversion of androgens to estrogens by inhibiting the aromatase enzyme, or
  • by blocking the estrogen receptors so that estrogen cannot bind and stimulate growth-related activity in breast and other cells.

Currently, the types (classes) of anti-estrogen drugs that are approved for the treatment of patients with breast cancer are called:

  • Aromatase inhibitors
  • Selective estrogen receptor modulators (SERMs)
  • Estrogen receptor antagonists

These three classes of drugs work by decreasing estrogen’s effects on the body, but they do so through different mechanisms.

Aromatase inhibitors: Aromatase inhibitors block the conversion of androgens to estrogen, and reduce estrogen levels in postmenopausal women. Currently, three anti-aromatase drugs[2],[3],[4] are approved for the treatment of postmenopausal women with breast cancer:

  • Femara® (letrozole)
  • Arimidex® (anastrozole)
  • Aromasin® (exemestane)

Femara and Arimidex are nonsteroidal aromatase inhibitors that bind reversibly to aromatase. Aromasin is a steroidal aromatase inhibitor that binds permanently to aromatase.

Selective Estrogen Receptor Modulators (SERM): SERMs block estrogen receptors within breast cells, thereby reducing estrogen-stimulated growth. Currently, tamoxifen is the most common SERM used for the hormonal treatment of breast cancer. However, tamoxifen is associated with side effects, including an increased risk of uterine cancer.

Estrogen Receptor Antagonist: Like SERMs, estrogen receptor antagonists work by preventing estrogen from stimulating the growth of estrogen receptor-positive cells. Faslodex® the first estrogen receptor antagonist, binds to and degrades estrogen receptors so that estrogen is no longer able to bind to the receptors and stimulate cellular growth.

Combination Therapy: A major hallmark of cancer cells is their ability to multiply rapidly. A new precision cancer medicine known as a cyclin-dependent kinases (CDK) inhibitor interferes with this process by blocking the activity of enzymes known as CDKs, particularly CDK 4 and CDK 6, that help to regulate cell division. Combining a CDK inhibitor with another anti-estrogen drug delays the time to cancer progression and prolongs survival.[5] CDK inhibitors are indicated for the treatment of HR+, HER2- advanced or metastatic breast cancer in combination with an anti-estrogen drug.

  • Verzenio (abemaciclib)
  • Kisqali (ribociclib)
  • Ibrance (palbociclib)

What Are the Side Effects of Hormonal Therapy?

Tamoxifen: Tamoxifen is associated with some side effects similar to symptoms of menopause, which include hot flashes, irregular menstrual periods and vaginal discharge or bleeding. Not all women will experience these symptoms. More serious side effects can also occur as a result of long-term use of tamoxifen. There is a small increase in the number of blood clots in individuals taking tamoxifen. Individuals taking tamoxifen have a slightly increased risk of developing cataracts. In addition, tamoxifen appears to increase a woman’s risk of developing uterine cancer by about 2-3 times that of the general population.[6],[7],[8],[9] This risk of uterine cancer is similar to that for women taking postmenopausal estrogen replacement therapy. Since the majority of uterine cancers can be detected at an early stage when they are highly curable, the overall benefit of anti-estrogen treatment in breast cancer patients probably outweighs the risk of uterine cancer. All women who have a uterus and are receiving anti-estrogen therapy should undergo regular gynecologic examinations.

The most common side effects caused by tamoxifen are

  • Hot flashes
  • Vaginal dryness
  • Discharge or Irritation
  • Decreased interest in sex.

These side effects are not usually serious, but they can be bothersome. Other side effects that are rare but are more dangerous include:

  • Overgrowth of the lining of the uterus (endometrial hyperplasia).
  • Cancer of the lining of the uterus (Endometrial cancer).
  • An increased risk of blood clots (in the legs (deep vein thrombosis and the lungs (pulmonary embolism).
  • A small increased chance of stroke.
  • Ovarian cysts
  • An increased risk of eye cataracts.

Aromatase inhibitors: Possible side effects of AIs include joint pain and decreased bone density. In fact, as many as half of women on AI therapy experience joint pain, and 20% become non-compliant with their AI therapy because of side effects.

The origin of AI-associated joint pain is unclear. There are no effective supportive care therapies to mitigate AI-associated joint pain and premature discontinuation of AI therapy may adversely affect breast cancer outcomes. Overall two-thirds of the women with AI-associated joint pain appear to have resolution or improvement of their symptoms once AI therapy was discontinued.

For women whose joint pain is significantly affecting quality of life, it is important to discuss quality of life factors, side effects and benefits of staying on therapy with their physician in order to make an informed treatment decision.[10],[11]

In a study known as the Intergroup Exemestane Study, postmenopausal women who had received two-to-three years of tamoxifen were assigned either to continue on tamoxifen or to switch to the aromatase inhibitor Aromasin® (exemestane). Women who switched to Aromasin had improved survival, but also experienced a minor loss of bone mineral density in the lumbar spine.[12] Women who are treated with aromatase inhibitors may wish to talk with their doctor about bone health.

Hormonal Therapy Treatment of Early-stage Breast Cancer

The use of hormonal therapy appears to benefit all women with hormone receptor-positive early-stage breast cancer. The primary benefit is a reduction in the risk of cancer recurrence.

For premenopausal women, tamoxifen remains the mainstay of hormonal therapy for early-stage breast cancer.[13] Tamoxifen is typically used for a period of five years. Suppression of ovarian hormone production, through surgical removal of the ovaries, radiation to the ovaries, or drugs such as leuteinizing hormone releasing hormone (LHRH) agonists, is another approach to hormonal therapy that may be incorporated into the treatment of premenopausal breast cancer patients.

For postmenopausal women, use of an aromatase inhibitor (either alone or sequentially with tamoxifen) appears to produce better outcomes than tamoxifen alone. When considering how best to use aromatase inhibitors in the treatment of postmenopausal breast cancer, researchers have considered several possibilities: aromatase inhibitors could be used for extended hormonal therapy, after a woman has completed tamoxifen treatment;[14] women could be switched to aromatase inhibitors after a brief (two to three year) period of tamoxifen therapy;[15] or aromatase inhibitors could be used in place of tamoxifen as initial hormone therapy.[16],[17] While it’s still uncertain which of these approaches is best, each of them appears to produce better outcomes than use of tamoxifen alone.

The benefits of hormonal therapy for women with estrogen receptor-positive breast cancer also apply to women with ductal carcinoma in situ (DCIS). Ductal carcinoma in situ (DCIS) is the earliest possible clinical diagnosis of breast cancer and is frequently diagnosed with screening mammography.[18]

Hormonal Therapy Treatment of Metastatic or Recurrent Breast Cancer

When breast cancer occurs outside of the breast in the bones, lungs, liver or other organs, it is referred to as metastatic. Patients with breast cancer may also experience a recurrence of cancer after initial treatment with hormonal therapy. Patients with newly diagnosed metastatic breast cancer benefit from initial treatment with hormonal therapy and those with recurrent cancer may benefit from switching to a different hormonal therapy. Hormonal therapy for advanced breast cancer differs depending on whether it is being administered as:

  • Initial treatment of metastatic breast cancer
  • Hormonal therapy after prior tamoxifen
  • Hormonal therapy after prior anti-aromatase drugs

Initial Treatment of Metastatic Breast Cancer

For premenopausal women, initial treatment of metastatic breast cancer historically used tamoxifen or an AI.[19] More recent studies however have shown that the CDK inhibitor Kisqali in combination with tamoxifen or an AI plus goserelin improved time of survival without cancer progression to 23.8 months compared to 13.0 months for tamoxifen or an aromatase inhibitor plus goserelin.[11]

For postmenopausal women, initial treatment with an aromatase inhibitor appears to result in more anti-cancer response and/or delays in cancer progression than treatment with tamoxifen[20], and the CDK inhibitor medications[21] when combined with an AI are superior to treatment with an AI alone. For example; the CDK inhibitor Verzenio demonstrated a greater than 28-month median progression-free survival (PFS) in patients who received initial endocrine-based therapy for metastatic disease compared to 14.8 months for treatment with an AI alone.

Treatment of Patients with Advanced Breast Cancer That Have Failed Prior Hormonal Therapy

For individuals with metastatic breast cancer that has stopped responding to tamoxifen, or an AI clinical trials have demonstrated that combination therapy with a CDK inhibitor and an AI can further prolong survival. For example the CDK inhibitor Ibrance when combined with Faslodex nearly doubles the duration of survival when compared to an AI alone.[22]

The antiestrogen drug Faslodex has been approved for the treatment of postmenopausal, estrogen receptor-positive metastatic breast cancer that has progressed following other anti-estrogen therapy.[23]

Can Hormonal Therapy Reduce the Risk of Developing Breast Cancer?

Drugs that block the effects of estrogen have been shown to reduce the risk of breast cancer in women at high risk of the disease. Two drugs that have been approved for breast cancer risk reduction in certain groups of women are tamoxifen and Evista® (raloxifene). Tamoxifen is approved for breast cancer risk reduction in women who are at high risk of the disease (including high-risk premenopausal women). Evista – originally approved for the prevention and treatment of osteoporosis — is approved for breast cancer risk reduction in postmenopausal women with osteoporosis or postmenopausal women at high risk of breast cancer.

To directly compare Evista to tamoxifen in the prevention of breast cancer in high-risk women, researchers conducted a clinical trial known to as the STAR trial (The NSABP Study of Tamoxifen and Raloxifene [STAR] P-2 Trial).[24] The study found that Evista is as effective as tamoxifen in reducing the risk of invasive breast cancer in high-risk postmenopausal women, but may be less effective in reducing the risk of noninvasive breast cancers such as ductal carcinoma in situ (DCIS). Evista carried a lower risk of blood clots and cataracts than tamoxifen, but is not without side effects. Evista has been found to increase the risk of blood clots and fatal strokes in women with coronary heart disease or at risk for coronary heart disease.[25]

Are There Other Benefits Associated with Hormonal Therapy?

Hormonal treatment may offer additional benefits beyond the treatment of cancer. Although tamoxifen acts against the effects of estrogen in breast tissue, it acts like estrogen in certain other body systems. Tamoxifen may help to lower blood cholesterol and reduce the rate of bone loss (osteoporosis). Two clinical studies have reported that women treated with tamoxifen had a lower risk of cardiac disease than women not treated with tamoxifen.[26] In addition, raloxifene (Evista®), another selective estrogen receptor modulator (SERM), is FDA-approved for the prevention and treatment of osteoporosis and appears to reduce the risk of breast cancer.[27]

Precision Cancer Medicine for Breast Cancer

The purpose of precision cancer medicine is not to categorize or classify cancers solely by site of origin, but to define the genomic alterations in the cancer’s DNA that are driving that specific cancer. Precision cancer medicines can be used both instead of and in addition to chemotherapy to improve treatment. Precision cancer medicine utilizes molecular diagnostic testing, including DNA sequencing, to identify cancer-driving abnormalities in a cancer’s genome. Once a genetic abnormality is identified, a specific targeted therapy can be designed to attack a specific mutation or other cancer-related change in the DNA programming of the cancer cells. Precision cancer medicine uses targeted drugs and immunotherapies engineered to directly attack the cancer cells with specific abnormalities, leaving normal cells largely unharmed.

By testing an individual’s breast cancer for specific unique biomarkers doctors continue to develop new precision medicines. Individuals not previously tested undergo genomic testing to determine whether newer precision cancer medicines are a treatment option

Genetic Mutations

Not all breast cancer cells are alike. They may differ from one another based on what genes have mutations. Molecular testing is performed to test for certain genetic mutations or the proteins they produce because the results can help select treatment including newer precision cancer medicines designed to attack specific colon cancer cells with specific genetic mutations.

HER2 status: The HER2 pathway is a biological pathway involved in cellular replication and growth. Approximately 20-25% of breast cancers overexpress the HER2 protein and are referred to as HER2-positive. Several precision cancer medicines target and block the HER2-protein, and are used for the treatment of both early-stage and more advanced HER2-positive breast cancer.

  • Herceptin (trastuzumab) was the first precision cancer medicine developed to target HER2-positive breast cancer and is used in both early and advanced stage cancers.
  • Nerlynx™ (neratinib) is a tyrosine kinase inhibitor that targets the HER1, HER2, and HER4 pathways and is approved is approved for the extended adjuvant treatment of early stage HER2-positive breast cancer following adjuvant Herceptin-based therapy.[2]
  • Kadcyla™ (ado-trastuzumab emtansine) is an antibody-drug conjugates that combines Herceptin and a chemotherapy drug that interferes with cancer cell growth. Kadcyla delivers Herceptin and chemotherapy directly to HER2-positive cells.[3]
  • Perjeta® (pertuzumab) targets HER2 and is approved for the treatment of early stage HER2-positive breast cancer before surgery.[4]

Cyclin Dependent Kinase Inhibitors (CDK) interfere with cancer cells ability to multiply rapidly by blocking the activity of CDK enzymes, particularly CDK 4 and CDK 6 that help to regulate cell division. CDK inhibitors are usually combined with hormonal therapy, which works by preventing hormones from binding with their respective receptors on the cancer cells.[5]

  • Verzenio (abemaciclib) when administered in combination with hormonal therapy delays the time to cancer progression in women with hormone-receptor-positive (HR+) HER2 negative advanced breast cancer.[5]
  • Kisqali (ribociclib) when combined with hormone therapy improves survival without cancer progression in premenopausal women. Premenopausal breast cancer is a biologically distinct and more aggressive disease than postmenopausal breast cancer, and it is the leading cause of cancer death in women 20-59 years old.[6]
  • Ibrance (palbociclib) for women with HR-positive, HER2 -negative, advanced breast cancer.[7]

BRCA mutations: About three percent of breast cancers are in people who inherited BRCA mutations. Mutations in the BRCA gene raise the risk of cancer because they make the body less likely to repair damage to its DNA, making the mutations that lead to cancer more likely. Poly ADP-ribose polymerase (PARP) inhibitors block enzymes involved in repairing damaged DNA. By disrupting a cancer cells’ ability to repair itself PARP inhibitors slow uncontrolled growth and replication of cancer cells.

  • Lynparza (olaparib) is the first PARP inhibitor approved for use in breast cancer. Lynparza was demonstrated to be superior to chemotherapy for treatment of HER2-negative advanced breast cancer patients who have a BRCA mutation.[8]

Checkpoint Inhibitors are a novel precision cancer immunotherapy that helps to restore the body’s immune system in fighting cancer by releasing checkpoints that cancer uses to shut down the immune system. PD-1 and PD-L1 are proteins that inhibit certain types of immune responses, allowing cancer cells to evade detection and attack by certain immune cells in the body. A checkpoint inhibitor can block the PD-1 and PD-L1 pathway and enhance the ability of the immune system to fight cancer. By blocking the binding of the PD-L1 ligand these drugs restore an immune cells’ ability to recognize and fight the lung cancer cells. A diagnostic test to measure the level of PD-L1 is available.[9],[10]

  • Keytruda (pembrolizumab)
  • Opdivo (nivolumab)

Additional targets will continue to be identified and precision cancer medicines created to attack those targets. Patients should ensure they discuss the role of genomic testing and precision cancer medicines with their doctor and undergo molecular testing of their cancer tissue and potentially blood.

References

[1] Poggi MM, Danforth DN, Sciuto LC, et al. Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: the National Cancer Institute Randomized Trial. Cancer 2003;98(4): 697-702.

[2] Edge SB, Niland JC, Bookman MA, et al. Emergence of sentinel node biopsy in breast cancer as standard-of care in academic comprehensive cancer centers. Journal of the National Cancer Institute2003;95:1514-1521.

[3] Veronesi U, Paganelli G, Viale G, et al. A randomized comparison of sentinel-node biopsy with routine axillary dissection in breast cancer. The New England Journal of Medicine 2003;349:546-553.

[1] Lake DE, Hudis C. Aromatase Inhibitors in Breast Cancer: An Update. Cancer Control. 2002;9:490-498.

[2] Food and Drug Administration. FDA Oncology Tools Approval Summary for Femara® for Treatment of advanced breast cancer in postmenopausal women. Accessed March 29, 2002.

[3] Food and Drug Administration. FDA Oncology Tools Approval Summary for Arimidex® for Treatment of advanced breast cancer in postmenopausal women with disease progression following Nolvadex® therapy. Accessed March 29, 2002.

[4] Food and Drug Administration. FDA Oncology Tools Approval Summary for Aromasin® for Treatment of advance breast cancer in postmenopausal women whose disease has progressed following Nolvadex®therapy. Accessed March 29, 2002.

[5] Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors [published ahead of print May 23, 2016]. Cancer Discov. 2016;6:740-753.

[6] Pritchard KI, Paterson AHG, Paul NA, Zee B, Fine S, Pater J. Increased thromboembolic complications with concurrent Nolvadex® and chemotherapy in a randomized trial of adjuvant therapy for women with breast cancer. Journal of Clinical Oncology 1996;14:2731-2737.

[7] Love RR, Cameron L, Connell BL, Leventhal H. Symptoms associated with Nolvadex® treatment in postmenopausal women. Arch Intern Med 1991;151:1842-1847.

[8] Nolvadex®-associated eye toxicity. Bethesda, Md.: National Cancer Institute, January 27, 1997.

[9] Fisher B, Costantino JP, Redmond CK, Fisher ER, Wickerham DL, Cronin WM. Endometrial cancer in Nolvadex®-treated breast cancer patients: findings from the National Surgical Adjuvant Breast and Bowel Project (NSABP) B-14. Journal of the National Cancer Institute 1994;86:527-537.

[10] Burstein HJ. Aromatase inhibitor-associated arthralgia syndrome. Breast. 2007 Jun;16(3)223-34.

[11] Laroche M, Seniow M, Roche H, Ruyssen-Witrand A. Arthralgia Associated with Autoimmune Abnormalities under Aromatase Inhibitor Therapy: Outcome after Cessation of Treatment. Journal of Rheumatology. 43;10; 1945-1946. doi: 10.3899/jrheum.160254

[12] Coleman R, Banks L, Girgis S, et al. Skeletal effects of exemestane on bone mineral density, bone biomarkers, and fracture incidence in postmenopausal women with early breast cancer participating in the Intergroup Exemestane Study (IES): a randomised controlled study. Lancet Oncology . 2007;8:119-27.

[13] Davidson NE, Osborne CK. Adjuvant Endocrine Therapy for Early-stage Breast Cancer. In: Govindan R, ed. American Society of Clinical Oncology 2007 Educational Book. Alexandria, VA: American Society of Clinical Oncology; 2007:96-99.

[14] Goss P, Ingle J, Martino S, et al. Randomized Trial of Letrozole Following Tamoxifen as Extended Adjuvant Therapy in Receptor-Positive Breast Cancer: Updated Findings from NCIC CTG MA.17. Journal of the National Cancer Institute. 2005; 97: 1262-1271.

[15] Coombes RC, Paridaens R, Jassem J et al. First Mature Analysis of the Intergroup Exemestane Study: a Randomized Trial in Disease-free, Postmenopausal Patients with Early Breast Cancer Randomized to Continue Tamoxifen or to Switch to Exemestane Following an Initial 2-3 Years of Adjuvant Tamoxifen. Presented at the 2006 ASCO Annual Meeting. Abstract #LBA527.

[16] Howell A, Cuzick J, Baum M et al. Results of the ATAC (Arimidex, Tamoxifen, Alone or in Combination) Trial after Completion of 5 Years’ Adjuvant Treatment for Breast Cancer. The Lancet. 2005;365:60-2.

[17] The Breast International Group (BIG) 1-98 Collaborative Group. A Comparison of Letrozole and Tamoxifen in Postmenopausal Women with Early Breast Cancer. New England Journal of Medicine. 2005;353:2747-57.

[18] Fisher B, Dignam J, Wolmark N et al. Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet. 1999;353:1993-2000.

[19] Klijn JGM, Blamey RW, Boccardo F, Tominaga T, Duchateau L, Sylvester R. Combined tamoxifen and leuteinizing hormone-releasing hormone (LHRH) agonist versus LHRH agonist alone in premenopausal advanced breast cancer. Journal of Clinical Oncology. 2001;19:343-353.

[20] Tripathy D, Sohn J, Im S, et al. First-line ribociclib or placebo combined with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized Phase III MONALEESA-7 trial. Presented at the San Antonio Breast Cancer Symposium (SABCS), December 6, 2017, San Antonio, Texas (abstract#S2-05).

[21] Altundag K, Ibrahim NK. Aromatase Inhibitors and Breast Cancer: An Overview. The Oncologist. 2006;11:553-562.

[22] Turner NC, Ro J, André F, et al. Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer. New England Journal of Medicine. June 1, 2015DOI: 10.1056/NEJMoa1505270.

[23] Vogel VG, Costantino JP, Wickerham DL et al. Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes. Journal of the American Medical Association. 2006;295:(doi:10.1001/jama.295.23.joc60074).

[24] Barrett-Connor E, Mosca L, Collins P, et al. Effects of Raloxifene on Cardiovascular Events and Breast Cancer in Postmenopausal Women. New EnglandJournal of Medicine. 2006; 355: 125-137.

[25] Rutqvist LE, Mattsson A. Cardiac and thromboembolic morbidity among postmenopausal women with early-stage breast cancer in a randomized trial of adjuvant Nolvadex®. Journal of the National Cancer Institute 1993;85:1398-1406.

[26] Vogel VG, Costantino JP, Wickerham DL et al. Effects of Tamoxifen vs Raloxifene on the Risk of Developing Invasive Breast Cancer and Other Disease Outcomes. Journal of the American Medical Association. 2006; 295:2727-41.

[1] Gelber RD, Goldhirsch A, Piccart M, et al. HERA TRIAL: 2 years versus 1 year of trastuzumab after adjuvant chemotherapy in women with HER2-positive early breast cancer at 8 years of median follow up. Presented at the 37th Congress of the European Society for Medical Oncology (ESMO), Vienna, Austria, September 28-October 2, 2012. Abstract LBA6.

[2] businesswire.com/news/home/20170908005162/en/

[3] FDA approves new treatment for late-stage breast cancer. [FDA News Release]. U.S. Food and Drug Administration website. Available at:

[4] FDA approves Perjeta for neoadjuvant breast cancer treatment. [FDA Announcement]. U.S. Food and Drug Administration website. Available at:

[5] Patnaik A, Rosen LS, Tolaney SM, et al. Efficacy and safety of abemaciclib, an inhibitor of CDK4 and CDK6, for patients with breast cancer, non-small cell lung cancer, and other solid tumors [published ahead of print May 23, 2016]. Cancer Discov. 2016;6:740-753.

[6] Tripathy D, Sohn J, Im S, et al. First-line ribociclib or placebo combined with goserelin and tamoxifen or a non-steroidal aromatase inhibitor in premenopausal women with hormone receptor-positive, HER2-negative advanced breast cancer: results from the randomized Phase III MONALEESA-7 trial. Presented at the San Antonio Breast Cancer Symposium (SABCS), December 6, 2017, San Antonio, Texas (abstract#S2-05).

[7] Turner NC, Ro J, André F, et al. Palbociclib in Hormone-Receptor–Positive Advanced Breast Cancer. New England Journal of Medicine. June 1, 2015DOI: 10.1056/NEJMoa1505270.

[8] Robson M., Im SA., Senkus E., et al, OlympiAD: Phase III trial of olaparib monotherapy versus chemotherapy for patients (pts) with HER2-negative metastatic breast cancer (mBC) and a germline BRCA mutation (gBRCAm), Presented at the American Society of Clinical Oncology Annual Meeting, Chicago; June 2-6, 2017.

[9] mavendoctors.io/cancerconnect/breast-cancer/keytruda-halaven-may-be-effective-in-advanced-triple-negative-breast-cancer-B0WQut7JIUyw7L9M9v5mXQ/

[10] Tolaney SM, Kalinsky K, Kaklamani V, et al. Phase 1b/2 study to evaluate eribulin mesylate in combination with pembrolizumab in patients with metastatic triple-negative breast cancer. Presented at: 2017 San Antonio Breast Cancer Symposium; December 5-9, 2017; San Antonio, TX. Abstract PD6-13.

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