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. Show
 Factors that may affect breast cancer risk include the following:
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:
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. 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.
Symptoms and Signs of Breast CancerMany 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:
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:
Matted or fixed axillary lymph nodes suggest tumor spread, as does supraclavicular or infraclavicular lymphadenopathy. 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 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). 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
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.
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. 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. 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
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:
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*
Staging classification follows these models:
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. Ovarian suppression (eg, with leuprolide) has been used to minimize the destruction of ova by chemotherapy, but its efficacy is unproven. 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.
Poorer prognosis is associated with the following other factors:
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 Surgery involves mastectomy or breast-conserving surgery plus radiation therapy. Mastectomy is removal of the entire breast and includes the following types:
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. During both mastectomy and breast-conserving surgery, axillary lymph nodes are typically evaluated. Methods include
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 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
Disadvantages of contralateral prophylactic mastectomy include
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 is indicated after mastectomy if any 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. 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. 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:
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*
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
In patients with ER+ tumors, particularly low-risk tumors, endocrine therapy may be used instead of chemotherapy.
Patients with DCIS are often treated with daily oral tamoxifen. For postmenopausal women, an aromatase inhibitor is preferred. 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 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:
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. 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.
Chemoprevention with tamoxifen or raloxifene may be indicated for women with the following:
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.
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.
Click here for Patient Education Which patient has the highest risk for breast cancer?The main factors that influence your risk include being a woman and getting older. Most breast cancers are found in women who are 50 years old or older.
What increases the risk of developing breast cancer?Being overweight or obese
Having more fat tissue after menopause can raise estrogen levels and increase the chances of getting breast cancer. Women who are overweight also tend to have higher blood insulin levels. Higher insulin levels have been linked to some cancers, including breast cancer.
What is the greatest cause of breast cancer?Getting older is the most significant risk for developing breast cancer. Most breast cancers (80%) occur in women over the age of 50. And the older you are, the higher your risk.
Which of the following have been shown to increase the risk for development of breast cancer?Obesity. Studies have shown a clear association between obesity and increased risk of post-menopausal breast cancer. Because having more fat tissue can increase a woman's level of estrogen, it is important for a woman to attempt to control her weight, particularly after menopause.
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Which client is at greatest risk for the development of a cancerous breast lesion?
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