Prevention and Screening

Because of efforts to increase screening and early detection, most women have local disease at the time of diagnosis. ACS recommendations (https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html) begin annual screening for average-risk women at age 45, with the opportunity for screening to begin at age 40. Women should be familiar (https://www.cancer.org/cancer/breast-cancer/screening-tests-and-early-detection/american-cancer-society-recommendations-for-the-early-detection-of-breast-cancer.html) with the appearance and feel of their breasts and report any changes immediately to a healthcare provider.

Risk factors associated with breast cancer include (https://www.cancer.gov/types/breast/hp) older age, female gender, family or personal history of breast cancer, hereditary and genetic risk, history of radiation to the chest, alcohol and tobacco use, obesity, breast density, nulliparity, as well as breastfeeding, menstrual, and hormonal replacement factors.

Biomarkers

All newly diagnosed patients or those newly diagnosed with metastatic breast cancers should receive ER, PR, and HER2 testing. Those with ER- or PR-positive results are candidates for endocrine therapy such as an aromatase inhibitor (i.e., anastrozole, letrozole, and exemestane), fulvestrant, or tamoxifen. Tumors that express higher levels of HER2 benefit (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf) from an approved anti-HER2 treatments (e.g., trastuzumab, pertuzumab, lapatinib, trastuzumab emtansine).

Germline testing that identifies a pathogenic BRCA1 or BRCA2 variant may indicate a benefit from the addition of olaparib or talazoparib. HER2-negative tumors with PD-L1 expression may respond (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf) to atezolizumab with albumin-bound paclitaxel or alpelisib with fulvestrant.

Polygenetic risk scores with the 21 gene Oncotype Dx test are recommended for all node-negative breast cancers and can be considered in patients with one to three positive lymph nodes to better understand whether the addition of chemotherapy or other therapy will reduce their risk of recurrence. Risk-recurrence scores of 31 or higher indicate benefit from additional chemotherapy, scores less than 26 are not likely to respond to additional therapy, and those of 26–30 should be managed (https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf) on case-by-case basis.

Treatment

Treatment recommendations depend on the type of breast cancer although typically involve surgery (lumpectomy or mastectomy) with or without radiation. During surgery, lymph nodes are often assessed (https://www.cancer.gov/types/breast/patient/breast-treatment-pdq) using sentinel lymph node biopsy and removed as indicated. Chemotherapy, hormonal (endocrine) treatment, and other targeted and immunotherapies may be used (https://www.cancer.org/content/dam/cancer-org/research/cancer-facts-and-statistics/breast-cancer-facts-and-figures/breast-cancer-facts-and-figures-2019-2020.pdf) if the pathologic diagnosis, biomarkers, and stage warrant. For example, a patient with HER2+ disease would receive (https://www.cancer.gov/types/breast/patient/breast-treatment-pdq) a monoclonal antibody that targets the HER2 protein, such as the drug trastuzumab. Hormone-positive breast cancers may receive endocrine therapy with tamoxifen, an aromatase inhibitor, or a CDK 4/6 inhibitor in some settings. mTOR inhibitors, PI3K inhibitors, and drugs that target BRCA gene mutations are also used in certain situations. Review clinical trial options.

Side Effects and Toxicities

Surgical treatments, including lumpectomy, mastectomy, and lymph node assessment and removal, can lead to postoperative pain, lymphedema, and reduced range of motion. Radiation may induce skin irritation, tissue or lung fibrosis, pneumonitis, fatigue, and other side effects. Systemic chemotherapy can cause nausea or vomiting, myelosuppression, diarrhea or constipation, hair loss, peripheral neuropathy, and fatigue.

Targeted agents have unique side effects and risks for toxicities that should be routinely monitored. Review the package insert or other drug reference resources for each drug’s specific adverse events. Endocrine therapy may increase risk (https://doi.org/10.1188/20.ONF.374-399) for hot flashes, joint pain, bone loss, and in some cases blood clots. Monoclonal antibodies that target HER2-positive disease could affect cardiac function, so routinely monitor ejection fraction. CDK 4/6 inhibitors may cause (https://doi.org/10.1007/s11912-019-0769-3) low blood counts, fatigue, gastrointestinal toxicities, prolonged QT interval, and food or drug interactions. Prompt identification of toxicities should be reported and doses held or adjusted as indicated for severe adverse events.

Survivorship Care

Breast cancer survivors require coordinated care and communication across the cancer treatment team and other members of the patients care team using a survivorship treatment summary and care plan. ACS and the American Society of Clinical Oncology published the Breast Cancer Survivorship Care Guideline (https://ascopubs.org/doi/full/10.1200/jco.2015.64.3809) in 2016, which provides a comprehensive overview of care considerations.

Appropriate survivorship care factors in each patient’s unique treatment plan and its associated late and long-term side effects. The risk for surgery- or radiation-induced lymphedema increases (https://doi.org/10.3322/caac.21319) with the number of lymph nodes affected. Chemotherapy could cause long-term peripheral neuropathy, cognitive effects, and increased risk for secondary cancers. Systemic therapy with HER2 agents and some chemotherapy agents (e.g., anthracyclines) may contribute to cardiac damage; clinicians should routinely evaluate (https://doi.org/10.3322/caac.21319) signs and symptoms and make recommendations for prevention strategies, including healthy lifestyle modifications. Certain hormone therapies are associated (https://doi.org/10.1188/20.ONF.374-399) with sexual side effects, hot flashes, hyperlipidemia, and osteoporosis.

Additional factors for survivorship care include monitoring for disease recurrence, routine health monitoring, prevention and screening for second cancers, risk evaluation, genetic counseling, and healthy lifestyle. Patients should also be evaluated (https://doi.org/10.3322/caac.21319) for distress and other psychosocial effects related to the disease and treatment.