In the US, breast cancer is the 2nd leading cause of cancer death in white, black, Asian/Pacific Islander, American Indian/Alaska Native, and Hispanic women (after lung/bronchial cancer) but is the leading cause of cancer death among Hispanic women (1 General references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). About 276,480 new cases of invasive breast cancer and about 42,170 deaths from it are expected in 2020. In addition, about 48,530 new cases of in situ breast cancer are expected in 2020 (2 General references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ).
Male breast cancer accounts for about 1% of total cases; about 2620 new cases of invasive breast cancer and 520 deaths from it are expected in 2020 (2 General references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). In men, manifestations, diagnosis, and management are the same, although men tend to present later.
For women in the US, cumulative risk of developing breast cancer is 12% (1 in 8) by age 95. Much of the risk is incurred after age 60 (see table Risk of Being Diagnosed With Invasive Breast Cancer Risk of Being Diagnosed With Invasive Breast Cancer Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). These statistics can be misleading because most people die before age 95, and cumulative risk of developing the cancer in any 20-year period is considerably lower. Risk of dying of breast cancer is about 10% by 5 years after diagnosis (1 Risk factor references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ).
Factors that may affect breast cancer risk include the following:
Age: The strongest risk factor for breast cancer is age. Most breast cancers occur in women > 50.
Family history: Having a 1st-degree relative (mother, sister, daughter) with breast cancer doubles or triples risk of developing the cancer, but breast cancer in more distant relatives increases risk only slightly. When ≥ 2 1st-degree relatives have breast cancer, risk may be 5 to 6 times higher.
Breast cancer gene mutation: About 5 to 10% of women with breast cancer carry a mutation in one of the two known breast cancer genes, BRCA1 or BRCA2. The lifetime risk of developing breast cancer with a BRCA mutation is about 50 to 85%. The risk of developing breast cancer by age 80 is about 72% with a BRCA1 mutation and about 69% with a BRCA2 mutation. Women with BRCA1 mutations also have a 20 to 40% lifetime risk of developing ovarian cancer; risk among women with BRCA2 mutations is increased less. Women without a family history of breast cancer in at least two 1st-degree relatives are unlikely to carry this mutation and thus do not require screening for BRCA1 and BRCA2 mutations. Men who carry a BRCA2 mutation also have an increased risk of developing breast cancer. The mutations are more common among Ashkenazi Jews. Women with BRCA1 or BRCA2 mutations may require closer surveillance or preventive measures, such as taking tamoxifen or raloxifene or undergoing double mastectomy.
Personal history: Having had in situ or invasive breast cancer increases risk. Risk of developing cancer in the contralateral breast after mastectomy is about 0.5 to 1%/year of follow-up.
Gynecologic history: Early menarche, late menopause, or late first pregnancy increases risk. Women who have a first pregnancy after age 30 are at higher risk than those who are nulliparous.
Breast changes: History of a lesion that required a biopsy increases risk slightly. Women with multiple breast masses but no histologic confirmation of a high-risk pattern should not be considered at high risk. Benign lesions that may slightly increase risk of developing invasive breast cancer include complex fibroadenoma, moderate or florid hyperplasia (without atypia), sclerosing adenosis, and papilloma. Risk is about 4 or 5 times higher than average in patients with atypical ductal or lobular hyperplasia and about 10 times higher if they also have a family history of invasive breast cancer in a 1st-degree relative. Increased breast density seen on screening mammography is associated with an increased risk of breast cancer.
Lobular carcinoma in situ (LCIS): Having LCIS increases the risk of developing invasive carcinoma in either breast by about 25 times; invasive carcinoma develops in about 1 to 2% of patients with LCIS annually.
Use of oral contraceptives: Oral contraceptive use increases risk very slightly (by about 5 more cases per 100,000 women). Risk increases primarily during the years of contraceptive use and tapers off during the 10 years after stopping.
Hormone therapy Hormone Therapy Menopause is physiologic or iatrogenic cessation of menses (amenorrhea) due to decreased ovarian function. Manifestations may include hot flushes, night sweats, sleep disruption, and genitourinary... read more : Postmenopausal hormone (estrogen plus a progestin) therapy appears to increase risk modestly after only 3 years of use (2 Risk factor references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). After 5 years of use, the increased risk is about 7 or 8 more cases per 10,000 women for each year of use (about a 24% increase in relative risk). Use of estrogen alone does not appear to increase risk of breast cancer (as reported in the Women's Health Initiative). Selective estrogen-receptor modulators (eg, raloxifene) reduce the risk of developing breast cancer.
Radiation therapy: Exposure to radiation therapy before age 30 increases risk. Mantle-field radiation therapy for Hodgkin lymphoma about quadruples risk of breast cancer over the next 20 to 30 years.
Diet: Diet may contribute to development or growth of breast cancers, but conclusive evidence about the effect of a particular diet (eg, one high in fats) is lacking. Obese postmenopausal women are at increased risk, but there is no evidence that dietary modification reduces risk. For obese women who are menstruating later than normal, risk may be decreased.
Lifestyle factors: Smoking and alcohol may contribute to a higher risk of breast cancer. Women are counseled to stop smoking and to reduce alcohol consumption. In epidemiologic studies, alcohol intake is associated with a higher risk of breast cancer; however, causality is difficult to establish. The American Cancer Society recommends no more than one alcoholic drink a day for women.
The Breast Cancer Risk Assessment Tool (BCRAT), or Gail model Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more , can be used to calculate a women's 5-year and lifetime risk of developing breast cancer.
1. American Cancer Society: Survival Rates for Breast Cancer. Accessed on 8/31/20.
2. Writing Group for the Women's Health Initiative Investigators: Risks and benefits of estrogen plus progestin in healthy postmenopausal women: Principal results from the Women's Health Initiative randomized controlled trial. JAMA 288 (3):321–333, 2002.
Most breast cancers are epithelial tumors that develop from cells lining ducts or lobules; less common are nonepithelial cancers of the supporting stroma (eg, angiosarcoma, primary stromal sarcomas, phyllodes tumor).
Cancers are divided into carcinoma in situ and invasive cancer.
Carcinoma in situ is proliferation of cancer cells within ducts or lobules and without invasion of stromal tissue. There are 2 types:
Ductal carcinoma in situ (DCIS): About 85% of carcinoma in situ are this type. DCIS is usually detected only by mammography. It may involve a small or wide area of the breast; if a wide area is involved, microscopic invasive foci may develop over time.
Lobular carcinoma in situ (LCIS): LCIS is often multifocal and bilateral. There are 2 types: classic and pleomorphic. Classic LCIS is not malignant but increases risk of developing invasive carcinoma in either breast. This nonpalpable lesion is usually detected via biopsy; it is rarely visualized with mammography. Pleomorphic LCIS behaves more like DCIS; it should be excised to negative margins.
Invasive carcinoma is primarily adenocarcinoma. About 80% is the infiltrating ductal type; most of the remaining cases are infiltrating lobular. Rare types include medullary, mucinous, metaplastic, and tubular carcinomas. Mucinous carcinoma tends to develop in older women and to be slow growing. Women with these rare types of breast cancer have a much better prognosis than women with other types of invasive breast cancer.
Inflammatory breast cancer is a fast-growing, often fatal cancer. Cancer cells block the lymphatic vessels in breast skin; as a result, the breast appears inflamed, and the skin appears thickened, resembling orange peel (peau d’orange). Usually, inflammatory breast cancer spreads to the lymph nodes in the armpit. The lymph nodes feel like hard lumps. However, often no mass is felt in the breast itself because this cancer is dispersed throughout the breast.
Paget disease of the nipple Paget Disease of the Nipple Paget disease is a rare type of carcinoma that appears as a unilateral eczematous to psoriasiform plaque of the nipple and areola. It results from extension to the epidermis of an underlying... read more (not to be confused with the metabolic bone disease also called Paget disease) is a form of ductal carcinoma in situ that extends into the skin over the nipple and areola, manifesting with a skin lesion (eg, an eczematous or a psoriaform lesion). Characteristic malignant cells called Paget cells are present in the epidermis. Women with Paget disease of the nipple often have underlying invasive or in situ cancer.
Breast cancer invades locally and spreads through the regional lymph nodes, bloodstream, or both. Metastatic breast cancer may affect almost any organ in the body—most commonly, lungs, liver, bone, brain, and skin. Most skin metastases occur near the site of breast surgery; scalp metastases are uncommon.
Some breast cancers may recur sooner than others; recurrence can often be predicted based on tumor markers. For example, metastatic breast cancer may occur within 3 years in patients who are negative for tumor markers or occur > 10 years after initial diagnosis and treatment in patients who have an estrogen-receptor positive tumor.
Estrogen and progesterone receptors, present in some breast cancers, are nuclear hormone receptors that promote DNA replication and cell division when the appropriate hormones bind to them. Thus, drugs that block these receptors may be useful in treating tumors with the receptors. About two thirds of postmenopausal patients with cancer have an estrogen receptor–positive (ER+) tumor. Incidence of ER+ tumors is lower among premenopausal patients.
Another cellular receptor is human epidermal growth factor receptor 2 (HER2; also called HER2/neu or ErbB2); its presence correlates with a poorer prognosis at any given stage of cancer. In about 20% of patients with breast cancer, HER2 receptors are overexpressed. Drugs that block these receptors are part of standard treatment for these patients.
Many breast cancers are discovered as a mass by the patient or during routine physical examination or mammography. Less commonly, the presenting symptom is breast pain or enlargement or a nondescript thickening in the breast.
Paget disease of the nipple manifests as skin changes, including erythema, crusting, scaling, and discharge; these changes usually appear so benign that the patient ignores them, delaying diagnosis for a year or more. About 50% of patients with Paget disease of the nipple have a palpable mass at presentation.
A few patients with breast cancer present with signs of metastatic disease (eg, pathologic fracture, pulmonary dysfunction).
A common finding during physical examination is asymmetry or a dominant mass—a mass distinctly different from the surrounding breast tissue. Diffuse fibrotic changes in a quadrant of the breast, usually the upper outer quadrant, are more characteristic of benign disorders; a slightly firmer thickening in one breast but not the other may be a sign of cancer.
More advanced breast cancers are characterized by one or more of the following:
Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy.
Inflammatory breast cancer is characterized by peau d'orange, erythema, and enlargement of the breast, often without a mass. A nipple discharge is common. Inflammatory breast cancer has a particularly aggressive course.
All women should be screened for breast cancer (1 Screening references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). All professional societies and groups agree on this concept, although they differ on the recommended age at which to start screening and the precise frequency of screening.
Screening modalities include
In mammography, low-dose x-rays of both breasts are taken in 2 views (oblique and craniocaudal).
Mammography is more accurate in older women, partly because with aging, fibroglandular tissue in breasts tends to be replaced with fatty tissue, which can be more easily distinguished from abnormal tissue. Mammography is less sensitive in women with dense breast tissue, and some states mandate informing patients that they have dense breast tissue when it is detected by screening mammography. Women with dense breast tissue may require additional imaging tests (eg, breast tomosynthesis [3-dimensional mammography], MRI).
Screening mammography guidelines for women with average risk of breast cancer vary, but generally, screening starts at age 40, 45, or 50 and is repeated every year or two until age 75 or life expectancy is < 10 years (see table Recommendations for Breast Cancer Screening Mammography in Women With Average Risk Recommendations for Breast Cancer Screening Mammography in Women With Average Risk Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). Clinicians should make sure that patients understand what their individual risk of breast cancer is and ask patients what their preference for testing is.
The Breast Cancer Risk Assessment Tool (BCRAT), or Gail model, can be used to calculate a woman's 5-year and lifetime risk of developing breast cancer. A woman is considered at average risk if her lifetime risk of breast cancer is < 15%.
Concerns about when and how often to do screening mammography include
Only about 10 to 15% of abnormalities detected on screening mammography result from cancer—an 85 to 90% false-positive rate. False-negative results may exceed 15%. Many of the false-positives are caused by benign lesions (eg, cysts, fibroadenomas), but there are new concerns about detecting lesions that meet histologic definitions of cancer but do not develop into invasive cancer during a patient's lifetime.
Accuracy depends partly on the techniques used and experience of the mammographer. Some centers use computer analysis of digitized mammography images (full-field digital mammography) to help in diagnosis. Such systems may be slightly more sensitive for invasive cancers in women < 50 when results are interpreted by radiologists, but probably not when interpreted primarily via computer detection.
Breast tomosynthesis (3-dimensional mammography), done with digital mammography, increases the rate of cancer detection slightly and decreases the rate of recall imaging (2); this test is helpful for women with dense breast tissue. However, the test exposes women to almost twice as much radiation as traditional mammography.
Although mammography uses low doses of radiation, radiation exposure Risks of Medical Radiation Ionizing radiation (see also Radiation Exposure and Contamination) includes High-energy electromagnetic waves (x-rays, gamma rays) Particles (alpha particles, beta particles, neutrons) Ionizing... read more has cumulative effects on cancer risk. When radiologic screening is started at a young age, risk of cancer is increased.
Costs include not only the cost of imaging itself but the costs and risks of diagnostic tests needed to evaluate false-positive imaging results.
The value of routine clinical or breast self-examination remains controversial. Some societies such as the American Cancer Society and the US Preventive Services Task Force recommend against either modality for routine screening in average-risk women. Other societies including the American College of Obstetricians and Gynecologists advocate clinical and breast self-examination as important components of screening for breast cancer.
Clinical breast examination (CBE) is usually part of routine annual care for women > 40 (1 Screening references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). In the US, CBE augments rather than replaces screening mammography. However, in some countries where mammography is considered too expensive, CBE is the sole screen; reports on its effectiveness in this role vary.
Breast self-examination (BSE) alone has not been shown to reduce mortality rate, but evidence of its usefulness is mixed, and it is widely practiced. Because a negative BSE may tempt some women to forego mammography or CBE, the need for these procedures should be reinforced when BSE is taught. Patients should be instructed to do BSE on the same day each month. For menstruating women, 2 or 3 days after menses ends is recommended because breasts are less likely to be tender and swollen.
MRI is thought to be better than CBE or mammography for screening women with a high (eg, > 20%) risk of breast cancer, such as those with a BRCA gene mutation. For these women, screening should include MRI as well as mammography and CBE. MRI has higher sensitivity but may be less specific. MRI may be recommended for women with dense breast tissue as part of overall assessment that includes evaluation of risk.
1. The American College of Obstetricians and Gynecologists: Practice bulletin no. 122: Breast cancer screening. Obstet Gynecol 118 (2), part 1:372–382, 2011.
2. Friedewald SM, Rafferty EA, Rose SL, et al: Breast cancer screening using tomosynthesis in combination with digital mammography. JAMA 311 (24):2499–2507, 2014. doi: 10.1001/jama.2014.6095
When an abnormality is detected during a physical examination or by a screening procedure Screening Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more , testing is required to differentiate benign lesions from cancer. Because early detection and treatment of breast cancer improves prognosis, this differentiation must be conclusive before evaluation is terminated.
If advanced cancer is suspected based on physical examination, biopsy should be done first; otherwise, the approach is the same as evaluation for a breast mass Evaluation The term breast mass is preferred over lump for a palpably discrete area of any size. A breast mass may be discovered by patients incidentally or during breast self-examination or by the clinician... read more , which typically includes ultrasonography. All lesions that could be cancer should be biopsied. A prebiopsy bilateral mammogram may help delineate other areas that should be biopsied and provides a baseline for future reference. However, mammogram results should not alter the decision to do a biopsy if that decision is based on physical findings.
Percutaneous core needle biopsy is preferred to surgical biopsy. Core biopsy can be done guided by imaging or palpation (freehand). Routinely, stereotactic biopsy (needle biopsy guided by mammography done in 2 planes and analyzed by computer to produce a 3-dimensional image) or ultrasound-guided biopsy is being used to improve accuracy. Clips are placed at the biopsy site to identify it.
If core biopsy is not possible (eg, the lesion is too posterior), surgical biopsy can be done; a guidewire is inserted, using imaging for guidance, to help identify the biopsy site.
Any skin taken with the biopsy specimen should be examined because it may show cancer cells in dermal lymphatic vessels.
The excised specimen should be x-rayed, and the x-ray should be compared with the prebiopsy mammogram to determine whether all of the lesion has been removed. If the original lesion contained microcalcifications, mammography is repeated when the breast is no longer tender, usually 6 to 12 weeks after biopsy, to check for residual microcalcifications. If radiation therapy is planned, mammography should be done before radiation therapy begins.
After cancer is diagnosed, a multidisciplinary evaluation is usually done to plan further testing and treatment. The core multidisciplinary team typically includes a breast surgical oncologist, medical oncologist, and radiation oncologist plus other experts in cancer (tumor board).
Part of a positive biopsy specimen should be analyzed for estrogen and progesterone receptors and for HER2 protein.
Cells from blood or saliva should be tested for inherited gene mutations that predispose to breast cancer when
Family history includes multiple cases of early-onset breast cancer.
Ovarian cancer develops in patients with a family history of breast or ovarian cancer.
Breast and ovarian cancers occur in the same patient.
Patients have an Ashkenazi Jewish heritage.
Family history includes a single case of male breast cancer.
Breast cancer develops at age < 45.
The cancer does not have estrogen or progesterone receptors or overexpression of HER2 protein (triple negative breast cancer).
Some experts have recommended that genetic testing be offered to all patients with breast cancer (1 Diagnosis reference Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ).
For these tests, the best approach is to refer patients to a genetic counselor, who can document a detailed family history, choose the most appropriate tests, and help interpret the results.
Chest x-ray, a complete blood count (CBC), liver tests, and measurement of serum calcium levels should be done to check for metastatic disease.
An oncologist should be consulted to determine whether to measure serum carcinoembryonic antigen (CEA), cancer antigen (CA) 15-3, or CA 27-29 and whether bone scanning should be done.
For bone scanning, common indications include the following:
Abdominal CT is done if patients have any of the following:
Chest CT is done if patients have either of the following:
MRI is often used by surgeons for preoperative planning; it can accurately determine tumor size, chest wall involvement, and number of tumors.
Grading is based on histologic examination of the tissue taken during biopsy. Tumor grade describes how abnormal tumor cells and tissue look under a microscope.
Staging follows the TNM (tumor, node, metastasis) classification (see table Anatomic Staging of Breast Cancer Anatomic Staging of Breast Cancer* Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). Because clinical examination and imaging have poor sensitivity for nodal involvement, staging is refined during surgery, when regional lymph nodes can be evaluated. However, if patients have palpably abnormal axillary nodes, preoperative ultrasonography-guided fine needle aspiration or core biopsy may be done:
If biopsy results are positive, axillary lymph node dissection is typically done during the definitive surgical procedure. However, use of neoadjuvant chemotherapy may make sentinel lymph node biopsy possible if chemotherapy changes node status from N1 to N0. (Results of intraoperative frozen section analysis determine whether axillary lymph node dissection will be needed.)
If results are negative, a sentinel lymph node biopsy, a less aggressive procedure, may be done instead.
Staging classification follows the
The anatomic staging model, which is based on anatomy of the tumor and which is used in regions of the world where biomarkers cannot be routinely obtained (see table Anatomic Staging of Breast Cancer Anatomic Staging of Breast Cancer* Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more )
The prognostic staging model, which is based on anatomy of the tumor as well as status of biomarkers and which is predominantly used in the US
Patients with breast cancer should not become pregnant while being treated for breast cancer. However, all patients who wish to preserve fertility should be referred to a reproductive endocrinologist to discuss fertility preservation before systemic therapy is initiated.
Options for fertility preservation include
Type of breast cancer, anticipated treatment, and patient preferences affect the type of fertility preservation that can be used. ART may have adverse effects in patients with estrogen-receptor positive tumors.
Long-term prognosis depends on tumor stage. Nodal status (including number and location of nodes) correlates with disease-free and overall survival better than any other prognostic factor.
The 5-year survival rate (from the National Cancer Institute's Surveillance, Epidemiology, and End Results (SEER) Program) depends on cancer stage:
Poorer prognosis is associated with the following other factors:
Young age: Prognosis appears worse for patients diagnosed with breast cancer during their 20s and 30s than for patients diagnosed during middle age.
Larger primary tumor: Larger tumors are more likely to be node-positive, but they also confer a worse prognosis independent of nodal status.
High-grade tumor: Patients with poorly differentiated tumors have a worse prognosis.
Absence of estrogen and progesterone receptors: Patients with ER+ tumors have a somewhat better prognosis and are more likely to benefit from hormone therapy. Patients with progesterone receptors on a tumor may also have a better prognosis. Patients with both estrogen and progesterone receptors on a tumor may have a better prognosis than those who have only one of these receptors, but this benefit is not clear.
Presence of HER2 protein: When the HER2 gene (HER2/neu [erb-b2]) is amplified, HER2 is overexpressed, increasing cell growth and reproduction and often resulting in more aggressive tumor cells. Overexpression of HER2 is an independent risk factor for a poor prognosis; it may also be associated with high histologic grade, ER− tumors, greater proliferation, and larger tumor size, which are all poor prognostic factors.
Presence of BRCA gene mutations: For any given stage, patients with the BRCA1 gene mutation appear to have a worse prognosis than those with sporadic tumors, perhaps because they have a higher proportion of high-grade, hormone receptor–negative cancers. Patients with the BRCA2 gene mutation probably have the same prognosis as those without the mutation if the tumors have similar characteristics. With either gene mutation, risk of a 2nd cancer in remaining breast tissue is increased (to perhaps as high as 40%).
For more detailed information about treatment, see NCCN Clinical Practice Guideline: Breast Cancer.
For most types of breast cancer, treatment involves surgery, radiation therapy, and systemic therapy. Choice of treatment depends on tumor and patient characteristics (see table Treatment by Type of Breast Cancer Treatment by Type of Breast Cancer Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). Recommendations for surgery are evolving and include early referral to a plastic or reconstruction surgeon for oncoplastic surgery (which combines cancer removal with reconstruction of the breast).
Surgery involves mastectomy or breast-conserving surgery plus radiation therapy.
Mastectomy is removal of the entire breast and includes the following types:
Skin-sparing mastectomy: Spares the pectoral muscles and enough skin to cover the wound, making breast reconstruction much easier, and spares axillary lymph nodes
Nipple-sparing mastectomy: Same as skin-sparing mastectomy plus spares the nipple and areola
Simple mastectomy: Spares the pectoral muscles and axillary lymph nodes
Modified radical mastectomy: Spares the pectoral muscles and removes some axillary lymph nodes
Radical mastectomy: Removes axillary lymph nodes and the pectoral muscles
Radical mastectomy is rarely done unless the cancer has invaded the pectoral muscles.
Breast-conserving surgery involves determining the size of the tumor and the required margins (based on the tumor's size relative to the volume of the breast), then surgically removing the tumor with its margins. Various terms (eg, lumpectomy, wide excision, quadrantectomy) are used to describe how much breast tissue is removed.
For patients with invasive cancer, survival and recurrence rates with mastectomy do not differ significantly from those with breast-conserving surgery plus radiation therapy as long as the entire tumor can be removed.
Thus, patient preference can guide choice of treatment within limits. The main advantage of breast-conserving surgery plus radiation therapy is less extensive surgery and opportunity to keep the breast. In 15% of patients thus treated, cosmetic results are excellent. However, the need for total removal of the tumor with a tumor-free margin overrides cosmetic considerations. Consulting a plastic surgeon about oncoplastic surgery may help if patients have ptotic (sagging) breasts, while also achieving good resection margins.
Some physicians use preoperative chemotherapy to shrink the tumor before removing it and applying radiation therapy; thus, some patients who might otherwise have required mastectomy can have breast-conserving surgery.
During both mastectomy and breast-conserving surgery, axillary lymph nodes are typically evaluated. Methods include
ALND is a fairly extensive procedure that involves removal of as many axillary nodes as possible; adverse effects, particularly lymphedema, are common. Most clinicians now first do SLNB unless biopsy of clinically suspect nodes detected cancer; risk of lymphedema is less with SLNB. Routine use of ALND is not justified because the main value of lymph node removal is diagnostic, not therapeutic, and SLNB has ≥ 95% sensitivity for axillary node involvement.
For SLNB, blue dye and/or radioactive colloid is injected around the breast, and a gamma probe (and when dye is used, direct inspection) is used to locate the nodes the tracer drains into. Because these nodes are the first to receive the tracers, they are considered the most likely to receive any metastatic cells and are thus called sentinel nodes.
If any of the sentinel nodes contain cancer cells, ALND may be necessary, based on numerous factors such as
Some surgeons do frozen section analysis during mastectomy with SLNB and get prior agreement for ALND in case nodes are positive; others await standard pathology results and do ALND as a 2nd procedure if needed. Frozen section analysis is not routinely done with lumpectomy.
Impaired lymphatic drainage of the ipsilateral arm often occurs after axillary node removal (ALND or SLNB) or radiation therapy, sometimes resulting in substantial swelling due to lymphedema. Magnitude of the effect is roughly proportional to the number of nodes removed; thus, SLNB causes less lymphedema than ALND. The lifetime risk of lymphedema after ALND is about 25%. However, even with SLNB, there is a 6% lifetime risk of lymphedema. To reduce risk of lymphedema, practitioners usually avoid giving IV infusions on the affected side. Wearing compression garments and preventing infection in the affected limbs (eg, by wearing gloves during yard work) are important. Avoiding ipsilateral blood pressure measurement and venipuncture is sometimes also recommended, even though supporting evidence is minimal (2 Treatment references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ).
If lymphedema develops, a specially trained therapist must treat it. Special massage techniques used once or twice a day may help drain fluid from congested areas toward functioning lymph basins; low-stretch bandaging is applied immediately after manual drainage, and patients should exercise daily as prescribed. After the lymphedema lessens, typically in 1 to 4 weeks, patients continue daily exercise and overnight bandaging of the affected limb indefinitely.
Reconstructive procedures include the following:
Breast reconstruction can be done during the initial mastectomy or breast-conserving surgery or later as a separate procedure. Timing of surgery depends on patient preference as well as the need for adjuvant therapy such as radiation therapy. However, doing radiation therapy first limits the types of reconstructive surgery that can be done. Thus, consulting a plastic surgeon early during treatment planning is recommended.
Advantages of breast reconstruction include improved mental health in patients who have a mastectomy. Disadvantages include surgical complications and possible long-term adverse effects of implants.
Early consultation with a plastic surgeon should also be considered when lumpectomy (especially lower breast or upper inner quadrant lumpectomy) is being done. The best candidates for oncoplastic surgery (which combines cancer removal with reconstruction of the breast) are patients with ptotic (sagging) breasts. Contralateral mastopexy may improve symmetry.
Contralateral prophylactic mastectomy is an option for some women with breast cancer (eg, those with a genetic mutation conferring a high risk of breast cancer).
In women with lobular carcinoma in situ in one breast, invasive cancer is equally likely to develop in either breast. Thus, the only way to eliminate the risk of breast cancer for these women is bilateral mastectomy. Some women, particularly those who are at high risk of developing invasive breast cancer, choose this option.
Advantages of contralateral prophylactic mastectomy include
Decreased risk of contralateral breast cancer (especially in women in a family history of breast or ovarian cancer)
Improvement in survival in breast cancer patients with an inherited genetic mutation (eg, BRCA1 or BRCA2 mutation) and possibly in women diagnosed at age < 50 years
Decreased anxiety in some patients
Decreased need for cumbersome follow-up imaging
Disadvantages of contralateral prophylactic mastectomy include
Contralateral prophylactic mastectomy is not mandatory, even for patients with the highest risk of developing cancer in the contralateral breast. Close surveillance is a reasonable alternative.
Radiation therapy is indicated after mastectomy if either of the following is present:
In such cases, radiation therapy after mastectomy significantly reduces incidence of local recurrence on the chest wall and in regional lymph nodes and improves overall survival.
Radiation therapy after breast-conserving surgery significantly reduces incidence of local recurrence in the breast and in regional lymph nodes and may improve overall survival. However, if patients are > 70 and have early ER+ breast cancer, adding radiation therapy to lumpectomy plus tamoxifen may not be necessary; adding radiation therapy does not significantly decrease the rate of mastectomy for local recurrence or the occurrence of distant metastases nor increase the survival rate (3 Treatment references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ).
Adverse effects of radiation therapy (eg, fatigue, skin changes) are usually transient and mild. Late adverse effects (eg, lymphedema, brachial plexopathy, radiation pneumonitis, rib damage, secondary cancers, cardiac toxicity) are less common.
To improve radiation therapy, researchers are studying several new procedures. Many of these procedures aim to target radiation to the cancer more precisely and spare the rest of the breast from the effects of radiation.
(See also NCCN Clinical Practice Guideline: Breast Cancer.)
Patients with LCIS are often treated with daily oral tamoxifen. For postmenopausal women, raloxifene or an aromatase inhibitor is an alternative.
For patients with invasive cancer, chemotherapy is usually begun soon after surgery. If systemic chemotherapy is not required (see below), hormone therapy is usually begun soon after surgery plus radiation therapy and is continued for years. These therapies delay or prevent recurrence in almost all patients and prolong survival in some. However, some experts believe that these therapies are not necessary for many small (< 0.5 to 1 cm) tumors with no lymph node involvement (particularly in postmenopausal patients) because the prognosis is already excellent. If tumors are > 5 cm, adjuvant systemic therapy may be started before surgery.
Relative reduction in risk of recurrence and death with chemotherapy or hormone therapy is the same regardless of the clinical-pathologic stage of the cancer. Thus, absolute benefit is greater for patients with a greater risk of recurrence or death (ie, a 20% relative risk reduction reduces a 10% recurrence rate to 8% but a 50% rate to 40%). Adjuvant chemotherapy reduces annual odds of death (relative risk) on average by 25 to 35% for premenopausal patients; for postmenopausal patients, the reduction is about half of that (9 to 19%), and the absolute benefit in 10-year survival is much smaller.
Postmenopausal patients with ER– tumors benefit the most from adjuvant chemotherapy (see table Preferred Breast Cancer Adjuvant Systemic Therapy Preferred Breast Cancer Adjuvant Systemic Therapy* Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ). For ER+ breast cancer, predictive genomic testing of the primary breast cancer is being used increasingly to stratify risk in patients and to determine whether combination chemotherapy or hormone therapy alone is indicated. Common prognostic tests include
In the US, most women with breast cancer have ER+/PR+/HER- breast cancer with negative axillary nodes. In these women, a low or intermediate score on the 21-gene recurrence score assay predicts similar survival rates with chemotherapy plus hormone and with hormone therapy alone. Therefore, in this subset of women with breast cancer, neoadjuvant chemotherapy may not be necessary.
Combination chemotherapy regimens are more effective than a single drug. Dose-dense regimens given for 4 to 6 months are preferred; in dose-dense regimens, the time between doses is shorter than that in standard-dose regimens. There are many regimens; a commonly used one is ACT (doxorubicin plus cyclophosphamide followed by paclitaxel). Acute adverse effects depend on the regimen but usually include nausea, vomiting, mucositis, fatigue, alopecia, myelosuppression, cardiotoxicity, and thrombocytopenia. Growth factors that stimulate bone marrow (eg, filgrastim, pegfilgrastim) are commonly used to reduce risk of fever and infection due to chemotherapy. Long-term adverse effects are infrequent with most regimens; death due to infection or bleeding is rare (< 0.2%).
High-dose chemotherapy plus bone marrow or stem cell transplantation offers no therapeutic advantage over standard therapy and should not be used.
If tumors overexpress HER2 (HER2+), anti-HER2 drugs (trastuzumab, pertuzumab) may be used. Adding the humanized monoclonal antibody trastuzumab to chemotherapy provides substantial benefit. Trastuzumab is usually continued for a year, although the optimal duration of therapy is unknown. If lymph nodes are involved involvement, adding pertuzumab to trastuzumab improves disease-free survival. A serious potential adverse effect of both these anti-HER2 drugs is a decreased cardiac ejection fraction.
With hormone therapy (eg, tamoxifen, raloxifene, aromatase inhibitors), benefit depends on estrogen and progesterone receptor expression; benefit is
In patients with ER+ tumors, particularly low-risk tumors, hormone therapy may be used instead of chemotherapy.
Tamoxifen: This drug competitively binds with estrogen receptors. Adjuvant tamoxifen for 5 years reduces annual odds of death by about 25% in premenopausal and postmenopausal women regardless of axillary lymph node involvement; treatment for 2 years is not as effective. If tumors have estrogen receptors, treatment for 10 years appears to prolong survival and reduce recurrence risk compared with 5 years of treatment. Tamoxifen can induce or exacerbate menopausal symptoms but reduces incidence of contralateral breast cancer and lowers serum cholesterol. Tamoxifen increases bone density in postmenopausal women and may reduce risk of fractures and ischemic heart disease. However, it significantly increases risk of developing endometrial cancer Endometrial Cancer Endometrial cancer is usually endometrioid adenocarcinoma. Typically, postmenopausal vaginal bleeding occurs. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy, bilateral... read more ; reported incidence is 1% in postmenopausal women after 5 years of use. Thus, if such women have spotting or bleeding, they must be evaluated for endometrial cancer. Nonetheless, the improved survival for women with breast cancer far outweighs increased risk of death due to endometrial cancer. Risk of thromboembolism is also increased.
Aromatase inhibitors: These drugs (anastrozole, exemestane, letrozole) block peripheral production of estrogen in postmenopausal women. More effective than tamoxifen, these drugs are becoming the preferred treatment for early-stage hormone receptor–positive cancer in postmenopausal patients. Letrozole may be used in postmenopausal women who have completed tamoxifen treatment. Optimal duration of aromatase inhibitor therapy is uncertain. A recent trial showed that extending treatment to 10 years resulted in a lower rate of breast cancer recurrence and higher rate of disease-free survival. There was no change in overall survival and a higher rate of fractures and osteoporosis in patients treated for an extended time.
Raloxifene, although indicated for prevention, is not indicated for treatment.
Any indication of metastases should prompt immediate evaluation. Treatment of metastases increases median survival by 6 months or longer. These treatments (eg, chemotherapy), although relatively toxic, may palliate symptoms and improve quality of life. Thus, the decision to be treated may be highly personal.
Choice of therapy depends on the following:
Systemic hormone therapy or chemotherapy is usually used to treat symptomatic metastatic disease. Initially, patients with multiple metastatic sites outside the central nervous system (CNS) should be given systemic therapy. If metastases are asymptomatic, there is no proof that treatment substantially increases survival, and it may reduce quality of life.
Hormone therapy is preferred over chemotherapy for patients with any of the following:
In premenopausal women, tamoxifen is often used first. Reasonable alternatives include ovarian ablation by surgery, radiation therapy, and use of a luteinizing-releasing hormone agonist (eg, buserelin, goserelin, leuprolide). Some experts combine ovarian ablation with tamoxifen or an aromatase inhibitor. In postmenopausal women, aromatase inhibitors are being increasingly used as primary hormone therapy. If the cancer initially responds to hormone therapy but progresses months or years later, additional forms of hormone therapy (eg, progestins, the antiestrogen fulvestrant) may be used sequentially until no further response occurs.
The most effective chemotherapy drugs are capecitabine, doxorubicin (including its liposomal formulation), gemcitabine, the taxanes paclitaxel and docetaxel, and vinorelbine. Response rate to a combination of drugs is higher than that to a single drug, but survival is not improved and toxicity is increased. Thus, some oncologists use single drugs sequentially.
Anti-HER2 drugs (eg, trastuzumab, pertuzumab) are used to treat tumors that overexpress HER2. These drugs are effective in treating and controlling visceral metastatic sites. Trastuzumab is used alone or with hormone therapy, chemotherapy, or pertuzumab. Trastuzumab plus chemotherapy plus pertuzumab slows the growth of HER2+ metastatic breast cancer and increases survival more than trastuzumab plus chemotherapy (4 Treatment references Breast cancer most often involves glandular breast cells in the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more ).
Tyrosine kinase inhibitors (eg, lapatinib, neratinib) are being increasingly used in women with HER2+ tumors.
Radiation therapy alone may be used to treat isolated, symptomatic bone lesions or local skin recurrences not amenable to surgical resection. Radiation therapy is the most effective treatment for brain metastases, occasionally providing long-term control.
Palliative mastectomy is sometimes an option for patients with stable metastatic breast cancer.
IV bisphosphonates (eg, pamidronate, zoledronate) decrease bone pain and bone loss and prevent or delay skeletal complications due to bone metastases. About 10% of patients with bone metastases eventually develop hypercalcemia, which can also be treated with IV bisphosphonates.
For patients with metastatic breast cancer, quality of life may deteriorate, and the chances that further treatment will prolong life may be small. Palliation may eventually become more important than prolongation of life.
Cancer pain Pain Physical, psychologic, emotional, and spiritual distress is common among patients living with fatal illness, and patients commonly fear protracted and unrelieved suffering. Health care providers... read more can be adequately controlled with appropriate drugs, including opioid analgesics Opioid Analgesics Nonopioid and opioid analgesics are the main drugs used to treat pain. Antidepressants, antiseizure drugs, and other central nervous system (CNS)–active drugs may also be used for chronic or... read more . Other symptoms (eg, constipation, difficulty breathing, nausea) should also be treated.
Psychologic and spiritual counseling should be offered.
Patients with metastatic breast cancer should be encouraged to update their will and to prepare advance directives Advance Directives Advance directives are legal documents that extend a person's control over health care decisions in the event that the person becomes incapacitated. They are called advance directives because... read more , indicating the type of care they desire in case they are no longer able to make such decisions.
1. Giuliano AE, Hunt KK, Ballman KV, et al: Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: A randomized clinical trial. JAMA 305 (6):569-575, 2011. doi: 10.1001/jama.2011.90
2. NLN: Position Statement Paper by the National Lymphedema Network: Lymphedema Risk Reduction Practices. May 2010. Accessed 8/31/20.
3. Hughes KS, Schnaper LA, Berry D, et al: Lumpectomy plus tamoxifen with or without irradiation in women 70 years of age or older with early breast cancer. N Engl J Med 351 (10):971-977, 2004.
4. Swain SM, Baselga J, Kim SB, et al: Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372 (8):724-734, 2015. doi: 10.1056/NEJMoa1413513
Chemoprevention with tamoxifen or raloxifene may be indicated for women with the following:
Age > 35 and previous LCIS or atypical ductal or lobular hyperplasia
Presence of high-risk mutations (eg, BRCA1 or BRCA2 mutations, Li-Fraumeni syndrome)
Age 35 to 59 and a 5-year risk of developing breast cancer > 1.66%, based on the multivariable Gail model, which includes the women’s current age, age at menarche, age at first live childbirth, number of 1st-degree relatives with breast cancer, and results of prior breast biopsies
A computer program to calculate breast cancer risk by the Gail model is available from the National Cancer Institute (NCI) at 1-800-4CANCER and on the NCI web site. Recommendations of the U.S. Preventive Services Task Force (USPSTF) for chemoprevention of breast cancer are available at the USPSTF web site.
Patients should be informed of risks before beginning chemoprevention.
Risks of tamoxifen include
Risks are higher for older women.
Raloxifene appears to be about as effective as tamoxifen in postmenopausal women and to have a lower risk of endometrial cancer, thromboembolic complications, and cataracts. Raloxifene, like tamoxifen, may also increase bone density. Raloxifene should be considered as an alternative to tamoxifen for chemoprevention in postmenopausal women.
Breast cancer is the second leading cause of cancer death in women; cumulative risk of developing breast cancer by age 95 is 12%.
Factors that greatly increase risk include breast cancer in close relatives (particularly if a BRCA gene mutation is present), atypical ductal or lobular hyperplasia, lobular carcinoma in situ, and significant exposure to chest radiation therapy before age 30.
Screen women by doing clinical breast examination, mammography (beginning at age 50 and often at age 40), and, for women at high risk, MRI.
Factors suggesting a poorer prognosis include younger age, absence of estrogen and progesterone receptors, and presence of HER2 protein or BRCA gene mutations.
For most women, treatment requires surgical removal, lymph node sampling, systemic therapy (hormone therapy or chemotherapy), and radiation therapy.
Treat with hormone therapy (eg, tamoxifen, an aromatase inhibitor) if tumors have hormone receptors.
Consider treating metastatic disease to relieve symptoms (eg, with chemotherapy, hormone therapy, or, for bone metastases, radiation therapy or bisphosphonates), even though survival is unlikely to be prolonged.
Consider chemoprevention with tamoxifen or raloxifene for women at high risk.