With staging information, hormone receptor status, HER2 status, and results of any genetic testing, a treatment plan can be created (NCCN 2017b). For women with stage 0, I, II, or III cancer, the first goal is to remove the cancer surgically (PDQ Adult Treatment Editorial Board 2017; NCCN 2017b). Additional treatments like chemotherapy, endocrine therapy, and radiation can help destroy remaining cancer cells. For women with stage IV cancer, there is ongoing research about the value of surgery for prolonging life and about the best timing of surgery, and while metastatic breast cancer is unlikely to be cured, endocrine therapy, surgery, and radiation are used for long-term disease control (NCCN 2017a).
Many breast cancer patients begin their treatment with surgery to remove the tumor and any cancer in nearby lymph nodes (NCCN 2017b). For many women with stage I or II cancer, doctors often recommend a procedure called a lumpectomy. A lumpectomy is also referred to as a breast-conserving surgery, because only the tumor and the normal breast tissue immediately around it are removed (NCCN 2016). During and after the surgery, doctors will inspect the outer edges of the removed tumor to be sure that no cancer was left behind (Moran 2014; Gray 2017; Blohmer 2016). Some women are treated with chemotherapy before surgery to shrink their tumor and make it easier to remove (NCCN 2016).
A mastectomy is a surgery that completely removes the breast. A mastectomy may be necessary depending on the size or location of the tumor and risk factors for additional tumors (NCCN 2016). Some women feel more comfortable choosing mastectomy over lumpectomy (Hamelinck 2017; Gu 2017). If a woman with breast cancer has a family history of breast cancer or a BRCA1 or BRCA2 mutation, doctors may recommend removing both breasts (Eisemann 2018; King 2013; Yi 2010).
A mastectomy is a longer procedure than a lumpectomy (NCCN 2016). Recovery is slower, and the procedure leaves a larger scar. Doctors recommend arm and shoulder exercises to improve strength and mobility (Shamley 2005; Akoochakian 2017). Breast reconstruction is an option for women after surgery (Platt 2018). Please see the sidebar on Breast Reconstruction for more information.
During a lumpectomy or mastectomy procedure, surgeons will also check nearby lymph nodes for cancer (NCCN 2017b). In an axillary (armpit area) lymph node dissection, 10 or more lymph nodes are checked for cancer (NCCN 2016). Removing the lymph nodes may cause swelling called lymphedema if the lymph fluid can no longer drain properly (Dominick 2013). Lymphedema may occur within days of surgery or may develop years later (P.D.Q. Supportive Palliative Care Editorial Board 2002). Symptoms are managed with compression sleeves, physical therapy, bandaging, massage, and laser therapy (NCI 2015).
If there is no lymph node enlargement, then sentinel lymph node biopsy is the standard of care (Esposito 2017). With sentinel biopsy, a dye is used to determine which lymph node the tumor drains to. Then, only that node is dissected and checked for cancer cells (NCCN 2016). Sentinel node biopsies are less likely to cause lymphedema (McLaughlin 2013).
More general information about the use of surgery in treating cancer is available in the Cancer Surgery protocol.
Chemotherapy and HER2 Inhibitors
Some women are treated with chemotherapy before surgery to shrink the tumor or after surgery to try to destroy any remaining cancer cells in the body (NCCN 2016; NCCN 2017b; PDQ Adult Treatment Editorial Board 2017). Chemotherapy may reduce the chances that the cancer will return. The need for chemotherapy is determined by many factors, such as the size of the tumor. Chemotherapy may not be needed for certain histological types of breast cancer or if the tumor is small or has not spread. Molecular testing together with gene panels are often helpful in guiding the need for chemotherapy (NCCN 2016; NCCN 2017b).
For women who do need chemotherapy, the selection of drugs and the dosing regimen can be adjusted based on risk factors (NCCN 2017b). Some studies have suggested that three to six months of chemotherapy is preferable over longer durations (Davidson 2016). Chemotherapy drugs are usually given in combinations to target cancer cells in more than one way and decrease the development of resistance (NCCN 2016; Curigliano 2017; Yardley 2013). Anthracyclines (doxorubicin [Adriamycin], epirubicin [Ellence]), taxanes (docetaxel [Taxotere], paclitaxel [Abraxane; Taxol]), vinca alkaloids (vinorelbine [Navelbine]), 5-fluorouracil, carboplatin (Paraplatin), and cyclophosphamide (Cytoxan) are some of the common types of chemotherapy (Davidson 2016; NCCN 2017b; PDQ Adult Treatment Editorial Board 2017).
Some breast cancers have changes that result in high levels of the growth factor receptor HER2 (Kourie 2017). Signaling through this receptor tells the cells to grow and divide. Trastuzumab (Herceptin) and pertuzumab (Perjeta) are two monoclonal antibody drugs that bind to HER2 and prevent signaling (NCCN 2016). Only women with tumors overexpressing HER2 are treated with these drugs. Trastuzumab emtansine (Kadcyla) is a version of trastuzumab linked to a chemotherapy drug called emtansine (Baselga 2017). The chemotherapy is a second way the drug can kill the target tumor cells (Kourie 2017; Baron 2015; Sau 2017).
Many of these chemotherapy drugs are designed to destroy cells that are actively growing and forming new cells (NCCN 2016). Although cancer cells will be killed, healthy normal cells may also be affected. Side effects are common and can be severe for some women (Davidson 2016). Gastrointestinal side effects include nausea, vomiting, and diarrhea (Fox 2017; Egger 2017). Blood cell counts can drop, leading to fatigue and immunosuppression (Nishijima 2016; Egger 2017). Cells in the hair follicles may be damaged, causing hair loss (NCCN 2016). The side effects will vary depending on the exact regimen of chemotherapy, and some can be managed with other medicines.
More general information about chemotherapy, including strategies to reduce chemotherapy side effects, is available in the Chemotherapy protocol.
Radiation uses high energy rays to damage the DNA inside cells. Treatment usually occurs after chemotherapy, or for women not treated with chemotherapy, soon after surgery (NCCN 2016; Boyages 2017). Modern techniques direct the radiation as much as possible to cancer cells to minimize side effects to healthy tissues. After a lumpectomy, radiation is targeted to part or all of the breast and may also target lymph nodes, depending on the risk of recurrence (NCCN 2017b; Kim, Algan 2017). After mastectomy, radiation is targeted to the chest wall and nearby lymph node sites (NCCN 2017b; Recht 2016).
The main form of radiation used to treat breast cancer is external beam radiation therapy or EBRT. A newer form of radiation delivery, called intensity-modulated radiation therapy, uses many small radiation beams carefully calculated to give the right dose of radiation to the right place, while minimizing radiation to surrounding, healthy tissues (NCCN 2017b; Chan 2017; NCCN 2016). Computed tomography (CT) imaging before the radiation procedure helps guide the radiation to the targeted area (NCCN 2016).
Toward the end of radiation treatment, patients may be treated with a higher dose of radiation, referred to as a radiation boost, to the area where the tumor was (PDQ Adult Treatment Editorial Board 2017; NCCN 2017b; Kindts 2017; Fiorentino 2015; NCCN 2016). The boost can be given by EBRT or internal radiation (also called brachytherapy) (Deng, Wu 2017; NCCN 2016). Internal radiation uses small radioactive seeds implanted directly into the breast tissue. After exposure, the seeds are removed (NCCN 2016).
Radiation therapy for breast cancer can cause a number of side effects such as damage to the skin of the irradiated area, fatigue, pain in the treated area, and damage to the heart or lungs. (Kole 2017; NCCN 2016; PDQ Adult Treatment Editorial Board 2017; Taylor 2017; Recht 2017).
For more complete information on radiation therapy techniques and side effects, see the Radiation Therapy protocol.
Most breast cancers overexpress receptors for the hormones estrogen and progesterone (Davidson 2016; Howlader 2014; Yip 2014). As with HER2, signaling through these receptors can tell the cancer cell to continue to grow and divide. Endocrine therapies are designed to disrupt this signaling in various ways (NCCN 2016). Endocrine therapy is recommended for most women whose cancer is estrogen-receptor positive (NCCN 2017b; NCCN 2016).
The type of endocrine therapy recommended to a patient will depend in part on her menopausal status. Before menopause, the ovaries are the main source of both estrogen and progesterone (NCCN 2016). Ovarian suppression is a strategy to reduce the amount of hormones in premenopausal women using luteinizing hormone-releasing hormone agonists such as goserelin (Zoladex) and leuprolide (Lupron) (NCCN 2016; Burstein 2016). Alternatively, the ovaries can be surgically removed. This approach is called ovarian ablation (NCCN 2016; Nourmoussavi 2017).
Both premenopausal and postmenopausal women may be treated with a type of drug called an antiestrogen, such as tamoxifen (NCCN 2016). Tamoxifen binds to the estrogen receptor to block estrogen signaling (NCCN 2016; Jameera Begam 2017). Postmenopausal women may also be treated with an aromatase inhibitor (letrozole [Femara], anastrozole [Arimidex], exemestane [Aromasin]). These drugs block the conversion of testosterone to estrogens (Davidson 2016; Olin 2014).
Studies suggested aromatase inhibitors may be more effective than tamoxifen for postmenopausal women (EBCTCG 2015; Xu, Liu 2011). Women diagnosed before menopause may also be candidates for treatment with aromatase inhibitors (NCCN 2016; NCCN 2017b). For these women, the production of estrogen by the ovaries may also be prevented by ovarian suppression (Francis 2015; Pagani 2014).
Women continue endocrine therapy long after diagnosis and initial treatment. A recent meta-analysis with data from over 60,000 women found that after five years of endocrine therapy, breast cancer can still recur. Even women with stage I cancer and no affected lymph nodes had a 13% chance of a distant recurrence (Pan 2017). A large trial involving almost 13,000 women found that 10 years of tamoxifen treatment reduced breast cancer recurrence and mortality compared with five years of treatment. In absolute numbers, breast cancer recurrence was 3.7% less likely among women who continued treatment (21.4% vs. 25.1%) and breast cancer mortality was 2.8% less likely (12.2% vs. 15%) (Davies 2013).
If cancers become resistant to hormone therapies or recur, another drug called everolimus (Afinitor) may be helpful (NCCN 2017b; Lousberg 2016; Steelman 2016). During endocrine therapy, some cancer cells find ways to proliferate that do not rely on hormone signaling (Fan 2015). Everolimus blocks some of these other pathways, making the cancer cells reliant on hormone signaling once again (Royce 2015). Everolimus in combination with the aromatase inhibitor exemestane (Aromasin) was found to significantly improve progression-free survival (NCCN 2017b; Baselga 2012).
Endocrine therapies may cause side effects similar to the symptoms of menopause, including hot flashes, vaginal dryness, and mood changes (NCCN 2016). Tamoxifen can increase the risk of blood clots and uterine cancer (NCCN 2016; Antimisiaris 2017). Women taking aromatase inhibitors have a higher risk for high cholesterol, high lipids, and high blood pressure than women taking tamoxifen (Foglietta 2017; NCCN 2016). Aromatase inhibitors can also weaken bones (NCCN 2016; Hadji 2017; Kristensen 2017). To protect patients from fractures, doctors may suggest treatment with a drug called denosumab (Xgeva) or a class of drugs called bisphosphonates (Tremblay 2018). Supplemental calcium and vitamin D can also help maintain long-term bone strength (Tremblay 2018; Cepa 2015).
Cyclin-dependent Kinase Inhibitors
Cyclin-dependent kinases 4 and 6 (CDK4 and CDK6) are two signaling proteins that may help cancer cells that are resistant to endocrine therapy to proliferate (PDQ Adult Treatment Editorial Board 2017). CDK 4/6 inhibitors include palbociclib (Ibrance), ribociclib (Kisqali), and abemaciclib (Verzenio) (Kwapisz 2017). These drugs may work well in combination with endocrine therapy. Indeed, clinical trial results have been promising. For instance, women with advanced breast cancer taking both palbociclib and the endocrine therapy fulvestrant (Faslodex) had a median progression-free survival time of 9.2 months compared with 3.8 months among women taking fulvestrant plus placebo (Turner 2015). Palbociclib and ribociclib are FDA approved for the treatment of metastatic or advanced breast cancer in combination with endocrine therapies (de Groot, Kuijpers 2017; Zangardi 2017; Ettl 2017). Additional trials have been or are being conducted to see whether these drugs can also help women at a different stage of treatment, such as before surgery (de Groot, Kuijpers 2017; Ma 2017).
Treatment of Bone Metastases
Among women with metastatic breast cancer, 55% have bone metastases (Body 2017). When cancer has spread to the bone, the bone cells called osteoclasts, which normally destroy small amounts of bone, to help keep them healthy, become overactive and cause damage (ACS 2016a). The damage may cause pain and can make the bones susceptible to breaks. Several medications are available to keep the osteoclasts under control and help strengthen the bones and reduce the risk of fractures. Bisphosphonates, including zoledronic acid (Zometa) and pamidronate (Aredia), and the monoclonal antibody denosumab (Xgeva) are both options (de Groot, Appelman-Dijkstra 2017; O'Carrigan 2017; ACS 2016a). In some cases, radiation or surgery are used to treat single sites of bone metastasis (ACS 2016a).
For many women, restoring their breasts after cancer surgery is important. Reconstructive surgery can either rebuild breasts after mastectomies or restore the appearance of breasts after lumpectomies. Recent studies demonstrated that reconstruction can relieve feelings of stress and anxiety in some women (Fanakidou 2017; McCarthy 2017).
Breast shape can be restored either by inserting implants under the muscle or by a tissue flap procedure, which transplants muscle tissue from another part of the body (PDQ Adult Treatment Editorial Board 2017; Opsomer 2018; Murphy 2018). Neither procedure is simple. In addition, radiation therapy, whether performed before or after surgery, can lead to a higher risk of problems with the implants (Nelson 2017; Ricci 2017; Shankar 2003). The reconstruction often looks and feels more natural after a tissue flap procedure, but this procedure generally requires more surgery than implants and creates more scars (ACS 2016b).
A novel alternative technique, called cell-assisted lipotransfer, has had promising results (Tsekouras 2017; Laloze 2017). The technique, pioneered by Dr. Kotaro Yoshimura in Japan, transplants fat cells enriched with stem cells to the breasts. The stem cells are included to help the fat cells survive and regenerate (Arshad 2016). Actress Suzanne Sommers sought out this treatment a few years ago and is happy with the results (Huget 2012). Life Extension Magazine® published two articles in 2011 titled “Cell-Assisted Lipotransfer Breast Restoration” and “Suzanne Somers Uses Novel Stem Cell Therapy During Breast Rejuvenation” that further explore this groundbreaking procedure. In initial clinical trials, this new procedure appears to be safe and effective (Arshad 2016; Ito 2017; Waked 2017).
A breast reconstruction procedure can be done at the same time as a total mastectomy or after treatment is completed (PDQ Adult Treatment Editorial Board 2017; Thamm 2018). Every patient and every treatment plan is unique. All members of the medical team—the surgeons, radiation oncologist, and medical oncologist—must carefully coordinate all aspects of care, including decisions on what type of reconstruction to use and when it should be conducted (NCCN 2017b; Panchal 2017).