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Breast Cancer


Lydia Choi

, MD, Karmanos Cancer Center

Last review/revision Mar 2022 | Modified Sep 2022
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Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis is confirmed by biopsy. Treatment usually includes surgical excision, often with radiation therapy, and with or without adjuvant chemotherapy, endocrine therapy, or both.

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 cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more General references ). In 2021 in women, there were

Male breast cancer accounts for about 1% of total cases. In 2021 in the US, there were 2650 new cases of invasive breast cancer and 530 deaths from it (2 General references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more General references ). In men, manifestations, diagnosis, and management are the same, although men tend to present at a later stage.

General references

Risk Factors for Breast Cancer


Factors that may affect breast cancer risk include the following:

The Breast Cancer Risk Assessment Tool (BCRAT), or Gail model Mammography Mammography , can be used to calculate a women's 5-year and lifetime risk of developing breast cancer.

Risk factor references

Pathology of Breast Cancer

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 be slow growing. Women with most of these rare types of breast cancer have a much better prognosis than women with other types of invasive breast cancer. However, the prognosis for women with metaplastic breast cancer is significantly worse than other types of ductal breast cancer.

Inflammatory breast cancer is a fast-growing, particularly aggressive, and 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 Paget Disease of the Nipple (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.

Pathophysiology of Breast 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.

Hormone receptors

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.

Breast cancer genes

BRCA1 and BRCA2 gene mutations increase the risk of developing breast cancer to 70% (1 Pathophysiology references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Pathophysiology references ). Prophylactic bilateral mastectomy reduces the risk of breast cancer by 90% and should be offered to women with a BRCA mutation. Other genetic mutations that increase the risk of developing breast cancer include mutations in CHEK2, PALB2, ATM, RAD51C, RAD51D, BARD1, and TP53, which are usually included in panel genetic testing (2 Pathophysiology references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Pathophysiology references ).

Pathophysiology references

Symptoms and Signs of Breast Cancer

Many breast cancers are discovered as a mass by the patient or during routine physical examination or mammography. Infrequently, the presenting symptom is breast enlargement or a nondescript thickening of the breast. Breast pain may be present but is almost never the sole presenting symptom of breast cancer.

Some types of breast cancer manifest with notable skin changes:

  • Paget disease of the nipple is associated with an underlying in situ or invasive carcinoma and 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.

  • Inflammatory breast cancer manifests as erythema and enlargement of the breast, often without a mass, and skin may be discolored or appear thickened, resembling orange peel (peau d’orange). A nipple discharge is common.

A few patients with breast cancer present with signs of metastatic disease (eg, pathologic fracture, abdominal pain, jaundice, dyspnea).

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:

  • Fixation of the mass to the chest wall or to overlying skin

  • Satellite nodules or ulcers in the skin

Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy.

Screening for Breast Cancer

Screening modalities include

  • Mammography (including digital and 3-dimensional)

  • Clinical breast examination (CBE) by health care practitioners

  • Magnetic resonance imaging (MRI) for high-risk patients


In mammography, low-dose x-rays of both breasts are taken in 2 views (oblique and craniocaudal).

Mammography is more accurate in women over 50, 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 Recommendations for Breast Cancer Screening Mammography in Women With Average Risk ). 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

  • Rate of false-positive positive results

  • Risks and costs

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% (3 Screening references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Screening references ). Many of the false-positives are caused by benign lesions (eg, cysts, fibroadenomas), but there are concerns about detecting lesions that meet histologic definitions of cancer but do not develop into invasive cancer during a patient's lifetime.

Breast tomosynthesis (3-dimensional mammography), done with digital mammography, increases the rate of cancer detection slightly and decreases the rate of recall imaging (4 Screening references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Screening references ); 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.

Breast examination

Clinical breast examination (CBE) is usually part of routine annual care for women > 40 (1 Screening references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Screening references ). In the US, CBE augments rather than replaces screening mammography. The American Cancer Society and the US Preventive Services Task Force recommend against screening with clinical breast examination (CBE); the American College of Obstetricians and Gynecologists recommends counseling patients about its diagnostic limitations (1 Screening references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Screening references , 2 Screening references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Screening references ). 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 as a screening method has not shown a benefit and may result in higher rates of unnecessary breast biopsy. The major professional organizations do not recommend it as part of routine screening. However, women should be counseled about breast self-awareness, and if they notice changes in how their breasts appear or feel (eg, masses, thickening, enlargement), they should be encouraged to have a medical evaluation.


MRI is used 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.

Screening references

  • 1. The American College of Obstetricians and Gynecologists: Practice bulletin no. 179: Breast cancer screening. Obstet Gynecol 130 (1), 241–243, 2017.

  • 2. U.S. Preventive Services Task Force: Screening for breast cancer: U.S. Preventive Services Task Force recommendation statement. Ann Intern Med 151 (10):716–726, W-236, 2009. doi:10.7326/0003 -4819-151-10-200911170-00008

  • 3. Nelson HD, Fu R, Cantor A, et al: Effectiveness of breast cancer screening: Systematic review and meta-analysis to Update the 2009 U.S. Preventive Services Task Force Recommendation. Ann Intern Med 164 (4):244–255, 2016. doi: 10.7326/M15-0969 Epub 2016 Jan 12.

  • 4. 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

Diagnosis of Breast Cancer

  • Screening by mammography, breast examination, and imaging (eg, ultrasonography)

  • Biopsy, including analysis for estrogen and progesterone receptors and for HER2 protein

Breast symptoms (eg, pain, nipple discharge) or abnormal findings (eg, mass) detected during breast examination are typically evaluated first with breast ultrasonography. If ultrasound results are abnormal or indeterminate, mammography is done. Biopsy is done if imaging findings suggest cancer or if a palpable breast mass or other physical findings suggest cancer, even if imaging results are negative. If advanced cancer is suspected based on physical examination, biopsy should be done first. A prebiopsy bilateral mammogram may help delineate other areas that should be biopsied and provides a baseline for future reference.

Pearls & Pitfalls

  • Biopsy should be done if physical findings (eg, palpable mass) suggest breast cancer, even if mammogram results are negative.


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.

Evaluation after cancer diagnosis

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.

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

  • Breast cancer develops at age < 45.

  • The cancer does not have estrogen or progesterone receptors or overexpression of HER2 protein (triple negative breast cancer).

  • Breast and ovarian cancers occur in the same patient.

  • Patients have lobular breast cancer plus a personal or family history of diffuse gastric cancer.

  • Family history includes multiple cases of early-onset breast cancer.

  • Family history of multiple cases of ovarian, pancreatic, or prostate cancer.

  • Patients have an Ashkenazi Jewish heritage.

  • Patient is male or family history includes any cases of male breast cancer.

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 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:

  • Bone pain

  • Elevated serum alkaline phosphatase

  • Stage III or IV cancer

Abdominal CT is done if patients have any of the following:

  • Abnormal liver test results

  • Abnormal abdominal or pelvic examination

  • Stage III or IV cancer

Chest CT is done if patients have either of the following:

  • Pulmonary symptoms such as shortness of breath

  • Stage III or IV cancer

MRI is often used by surgeons for preoperative planning; it can accurately determine tumor size, chest wall involvement, and number of tumors.

Grading and staging

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* Anatomic Staging of Breast Cancer* ). 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 these models:

  • 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* Anatomic Staging of Breast Cancer* )

  • 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


Fertility preservation

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

  • Assisted reproductive techniques (ART) with ovarian stimulation and oocyte and embryo cryopreservation

  • Ovarian or testicular tissue cryopreservation

Type of breast cancer, anticipated treatment, and patient preferences affect the type of fertility preservation that can be used. Ovarian suppression (eg, with leuprolide) has been used to minimize the destruction of ova by chemotherapy, but its efficacy is unproven.

Diagnosis reference

Prognosis for Breast Cancer

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:

  • Localized (confined to primary site): 99.0%

  • Regional (confined to regional lymph nodes): 85.8%

  • Distant (metastasized): 29.0%

  • Unknown: 57.8%

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.

  • Race: Breast cancer death rates from 2012 to 2016 were higher in the US in non-Hispanic Black females (28.9 per 100,000) than in non-Hispanic White females (20.6 per 100,000 [ 1 Prognosis reference Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Prognosis reference ]). Black women are diagnosed at a younger age compared with White women (median 59 versus 63 years) and are more likely to have triple negative disease.

  • 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 endocrine 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%).

Prognosis reference

Treatment of Breast Cancer

  • Surgery

  • Usually radiation therapy

  • Systemic therapy: Endocrine therapy, chemotherapy, or both

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 Treatment by Type of Breast Cancer ). 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 breasts. The need for total removal of the tumor with a tumor-free margin overrides any 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 neoadjuvant 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.

Lymph node evaluation

During both mastectomy and breast-conserving surgery, axillary lymph nodes are typically evaluated. Methods include

  • Axillary lymph node dissection (ALND)

  • Sentinel lymph node biopsy (SLNB)

ALND is a fairly extensive procedure that involves removal of as many axillary nodes as possible; adverse effects, particularly lymphedema, are common. Risk of lymphedema is increased for patients with a high preoperative body mass index (BMI ≥ 30) and for those with significant weight gain during and after breast cancer treatment (1 Treatment references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Treatment references ).

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 (3 Treatment references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Treatment references ).

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

Reconstructive procedures include the following:

  • Prosthetic reconstruction: Placement of a silicone or saline implant, sometimes after a tissue expander is used

  • Autologous reconstruction: Muscle flap transfer (using the latissimus dorsi, gluteus maximus, or the lower rectus abdominis) or muscle-free flap transfer

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

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

  • An almost two-fold increase in surgical complication rates

Contralateral prophylactic mastectomy is not mandatory for patients with the highest risk of developing cancer in the contralateral breast. Close surveillance is a reasonable alternative.

Radiation therapy

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 (4 Treatment references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Treatment references ).

Radiation therapy is indicated after mastectomy if any of the following is present:

  • The primary tumor is ≥ 5 cm.

  • Axillary nodes are involved.

  • Margins are positive for cancer in resected tissue.

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.

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.

Adjuvant chemotherapy or endocrine therapy

Chemotherapy or endocrine therapy delay or prevent recurrence in almost all patients and prolong survival in some. However, studies have shown that chemotherapy is 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.

Usual indications for chemotherapy are one or more of the following:

  • Estrogen receptor (ER) and progesterone receptor (PR)-negative

  • Human epidermal growth factor 2 (HER2) oncogene-positive

  • ER/PR+ and positive lymph nodes in a premenopausal patient

  • ER/PR+ and HER2- with high Oncotype Dx™ score

Relative reduction in risk of recurrence and death with chemotherapy or endocrine 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* Preferred Breast Cancer Adjuvant Systemic Therapy* ). 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 endocrine therapy alone is indicated. Common prognostic tests include

  • The 21-gene recurrence score assay (based on Oncotype Dx™)

  • The Amsterdam 70-gene profile (MammaPrint®)

  • The 50-gene risk of recurrence score (PAM50 assay)

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 endocrine therapy and with endocrine therapy alone. Therefore, in this subset of women with breast cancer, chemotherapy may not be necessary.

Chemotherapy is usually begun soon after surgery. If systemic chemotherapy is not required, endocrine therapy is usually begun soon after surgery and is continued for 5 to 10 years.

If tumors are > 5 cm, systemic therapy may be started before surgery.


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%).

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, 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 endocrine therapy (eg, tamoxifen, aromatase inhibitors), benefit depends on estrogen and progesterone receptor expression; benefit is

  • Greatest when tumors have expressed estrogen and progesterone receptors

  • Nearly as great when they have only estrogen receptors

  • Minimal when they have only progesterone receptors

  • Absent when they have neither receptor

In patients with ER+ tumors, particularly low-risk tumors, endocrine 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, it manifests as postmenopausal uterine bleeding. Diagnosis is by biopsy. Staging is surgical. Treatment requires hysterectomy... 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.

Patients with DCIS are often treated with daily oral tamoxifen. For postmenopausal women, an aromatase inhibitor is preferred.

Metastatic disease

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:

  • Hormone-receptor status of the tumor

  • Length of the disease-free interval (from remission to manifestation of metastases)

  • Number of metastatic sites and organs affected

  • Patient’s menopausal status

Systemic endocrine 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.

Endocrine therapy is preferred over chemotherapy for patients with any of the following:

  • ER+ tumors

  • A disease-free interval of > 2 years

  • Disease that is not immediately life threatening

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 endocrine therapy. If the cancer initially responds to endocrine therapy but progresses months or years later, additional forms of endocrine 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 endocrine 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 (5 Treatment references Breast cancers are most often epithelial tumors involving the ducts or lobules. Most patients present with an asymptomatic mass discovered during examination or screening mammography. Diagnosis... read more Treatment references ).

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.

End-of-life issues

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.

Psychologic and spiritual counseling should be offered.

Patients with metastatic breast cancer should be encouraged 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.

Treatment references

  • 1. Jammallo LS, Miller CL, Singer M, et al: Impact of body mass index and weight fluctuation on lymphedema risk in patients treated for breast cancer. Breast Cancer Res Treat 142 (1):59–67, 2013. doi: 10.1007/s10549-013-2715-7

  • 2. 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

  • 3. NLN: Position Statement Paper by the National Lymphedema Network: Lymphedema Risk Reduction Practices. May 2010. Accessed 8/31/20.

  • 4. 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.

  • 5. 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

Prevention of Breast Cancer

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.

Key Points

  • 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 (endocrine therapy or chemotherapy), and radiation therapy.

  • Treat with endocrine therapy (eg, tamoxifen, aromatase inhibitor) if tumors have hormone receptors.

  • Consider treating metastatic disease to relieve symptoms (eg, with chemotherapy, endocrine 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.

More Information

The following are some English-language resources that may be useful. Please note that THE MANUAL is not responsible for the content of these resources.

  • NCCN Clinical Practice Guideline: Breast Cancer: The National Comprehensive Cancer Network provides guidelines for the diagnosis, staging, and treatment of breast cancer (and other cancers)

  • U. S. Preventive Services Task Force: Breast Cancer: Medication Use to Reduce Risk: This web site provides the rationale of using drugs to reduce the risk of breast cancer in women at high risk and describes the risks of using these drugs.

  • National Cancer Institute: Breast Cancer: This web site discusses the genetics of breast and gynecologic cancers and the screening for and prevention and treatment of breast cancer. It also includes evidence-based information about supportive and palliative care.

Drugs Mentioned In This Article

Drug Name Select Trade
Nolvadex, Soltamox
CAMCEVI, Eligard, Fensolv, Lupron, Lupron Depot, Lupron Depot-Ped, Viadur
Adriamycin, Adriamycin PFS, Adriamycin RDF, Rubex
Cyclophosphamide, Cytoxan, Neosar
Fulphila, Fylnetra, Neulasta, Nyvepria, Stimufend, UDENYCA, Ziextenzo
Herceptin, Herzuma, KANJINTI, OGIVRI, Ontruzant , Trazimera
Gemzar, Infugem
Docefrez , Taxotere
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