1

General Information About Breast Cancer

This summary discusses primary epithelial breast cancers in women. The breast is rarely affected by other tumors such as lymphomas, sarcomas, or melanomas. Refer to the following PDQ summaries for more information on these cancer types:

Adult Hodgkin Lymphoma Treatment

Adult Soft Tissue Sarcoma Treatment

Melanoma Treatment

Breast cancer also affects men and children and may occur during pregnancy, although it is rare in these populations. Refer to the following PDQ summaries for more information:

Male Breast Cancer Treatment

Breast Cancer Treatment and Pregnancy

Unusual Cancers of Childhood Treatment

Incidence and Mortality

Estimated new cases and deaths from breast cancer (women only) in the United States in 2016:[1]

New cases: 246,660.

Deaths: 40,450.

Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 61,000 cases of in situ disease, 246,660 cases of invasive disease, and 40,450 deaths expected in 2016[1]. Thus, fewer than one of six women diagnosed with breast cancer die of the disease. By comparison, it is estimated that about 72,160 American women will die of lung cancer in 2016[1]. Men account for 1% of breast cancer cases and breast cancer deaths (refer to the Special Populations section in the PDQ summary on Breast Cancer Screening for more information).

Widespread adoption of screening increases breast cancer incidence in a given population and changes the characteristics of cancers detected, with increased incidence of lower-risk cancers, premalignant lesions, and ductal carcinoma in situ (DCIS). (Refer to the Ductal Carcinoma In Situ section in the Breast Cancer Diagnosis and Pathology section in the PDQ summary on Breast Cancer Screening for more information.) Population studies from the United States [2] and the United Kingdom [3] demonstrate an increase in DCIS and invasive breast cancer incidence since the 1970s, attributable to the widespread adoption of both postmenopausal hormone therapy and screening mammography. In the last decade, women have refrained from using postmenopausal hormones, and breast cancer incidence has declined, but not to the levels seen before the widespread use of screening mammography[4].

Anatomy

Anatomy of the female breast. The nipple and areola are shown on the outside of the breast. The lymph nodes, lobes, lobules, ducts, and other parts of the inside of the breast are also shown.

Risk and Protective Factors

Increasing age is the most important risk factor for breast cancer[2]. Other risk factors for breast cancer include the following:

Family health history[5].

Major inheritance susceptibility[6][7][8].

Germline mutation of the genes BRCA1 and BRCA2, and other breast cancer susceptibility genes[9][10][11][12][13].

Alcohol intake[14].

Breast tissue density (mammographic)[15][16].

Estrogen (endogenous):[17][18][19][20]

Menstrual history (early menarche/late menopause)[21][22][23].

Nulliparity.

Older age at first birth.

Hormone therapy history:[24]

Combination estrogen plus progestin hormone replacement therapy (HRT)[25][26][27][28].

Obesity[29][30].

Personal history of breast cancer[31].

Personal history of proliferative forms of benign breast disease[32][33][34][35][36][37][38].

Race[39][40].

Radiation exposure to the breast/chest[41][42].

Age-specific risk estimates are available to help counsel and design screening strategies for women with a family history of breast cancer[43][44].

Of all women with breast cancer, 5% to 10% may have a germline mutation of the genes BRCA1 and BRCA2[45]. Specific mutations of BRCA1 and BRCA2 are more common in women of Jewish ancestry[46]. The estimated lifetime risk of developing breast cancer for women with BRCA1 and BRCA2 mutations is 40% to 85%. Carriers with a history of breast cancer have an increased risk of contralateral disease that may be as high as 5% per year[47]. Male BRCA2 mutation carriers also have an increased risk of breast cancer[48].

Mutations in either the BRCA1 or the BRCA2 gene also confer an increased risk of ovarian cancer [48][49] or other primary cancers[48][49]. Once a BRCA1 or BRCA2 mutation has been identified, other family members can be referred for genetic counseling and testing[50][51][52][53]. (Refer to the PDQ summaries on Genetics of Breast and Gynecologic Cancers; Breast Cancer Prevention; and Breast Cancer Screening for more information.)

(Refer to the PDQ summary on Breast Cancer Prevention for more information about factors that increase the risk of breast cancer.)

Protective factors and interventions to reduce the risk of female breast cancer include the following:

Estrogen use (after hysterectomy)[54][55][56].

Exercise[57][58][59].

Early pregnancy[23][60][61].

Breast feeding[62].

Selective estrogen receptor modulators (SERMs)[63].

Aromatase inhibitors or inactivators[64][65].

Risk-reducing mastectomy[66].

Risk-reducing oophorectomy or ovarian ablation[67][68][69][70].

(Refer to the PDQ summary on Breast Cancer Prevention for more information about factors that decrease the risk of breast cancer.)

Screening

Clinical trials have established that screening asymptomatic women using mammography, with or without clinical breast examination, decreases breast cancer mortality. (Refer to the PDQ summary on Breast Cancer Screening for more information.)

Diagnosis

Patient evaluation

When breast cancer is suspected, patient management generally includes the following:

Confirmation of the diagnosis.

Evaluation of the stage of disease.

Selection of therapy.

The following tests and procedures are used to diagnose breast cancer:

Mammography.

Ultrasound.

Breast magnetic resonance imaging (MRI), if clinically indicated.

Biopsy.

Contralateral disease

Pathologically, breast cancer can be a multicentric and bilateral disease. Bilateral disease is somewhat more common in patients with infiltrating lobular carcinoma. At 10 years after diagnosis, the risk of a primary breast cancer in the contralateral breast ranges from 3% to 10%, although endocrine therapy decreases that risk[71][72][73]. The development of a contralateral breast cancer is associated with an increased risk of distant recurrence[74]. When BRCA1/BRCA2 mutation carriers were diagnosed before age 40 years, the risk of a contralateral breast cancer reached nearly 50% in the ensuing 25 years[75][76].

Patients who have breast cancer will undergo bilateral mammography at the time of diagnosis to rule out synchronous disease. To detect either recurrence in the ipsilateral breast in patients treated with breast-conserving surgery or a second primary cancer in the contralateral breast, patients will continue to have regular breast physical examinations and mammograms.

The role of MRI in screening the contralateral breast and monitoring women treated with breast-conserving therapy continues to evolve. Because an increased detection rate of mammographically occult disease has been demonstrated, the selective use of MRI for additional screening is occurring more frequently despite the absence of randomized, controlled data. Because only 25% of MRI-positive findings represent malignancy, pathologic confirmation before treatment is recommended. Whether this increased detection rate will translate into improved treatment outcome is unknown[77][78][79].

Prognostic Factors

Breast cancer is commonly treated by various combinations of surgery, radiation therapy, chemotherapy, and hormone therapy. Prognosis and selection of therapy may be influenced by the following clinical and pathology features (based on conventional histology and immunohistochemistry):[80]

The menopausal status of the patient.

The stage of the disease.

The grade of the primary tumor.

The estrogen receptor (ER) and progesterone receptor (PR) status of the tumor.

Human epidermal growth factor type 2 receptor (HER2/neu) overexpression and/or amplification.

The histologic type. Breast cancer is classified into a variety of histologic types, some of which have prognostic importance. For example, favorable histologic types include mucinous, medullary, and tubular carcinomas[81][82][83].

The use of molecular profiling in breast cancer includes the following:[84]

ER and PR status testing.

HER2/neu receptor status testing.

Gene profile testing by microarray assay or reverse transcription-polymerase chain reaction (e.g., MammaPrint, Oncotype DX).

On the basis of these results, breast cancer is classified as:

Hormone-receptor positive.

HER2 positive.

Triple negative (ER, PR, and Her2/neu negative).

Although certain rare inherited mutations, such as those of BRCA1 and BRCA2, predispose women to develop breast cancer, prognostic data on BRCA1/BRCA2 mutation carriers who have developed breast cancer are conflicting; these women are at greater risk of developing contralateral breast cancer.

Posttherapy Considerations

Hormone replacement therapy

After careful consideration, patients with severe symptoms may be treated with hormone replacement therapy. For more information, refer to the following PDQ summaries:

Breast Cancer Prevention

Hot Flashes and Night Sweats

Related Summaries

Other PDQ summaries containing information related to breast cancer include the following:

Breast Cancer Prevention

Breast Cancer Screening

Breast Cancer Treatment and Pregnancy

Genetics of Breast and Gynecologic Cancers

Male Breast Cancer Treatment

Unusual Cancers of Childhood Treatment (breast cancer in children)

References

1. American Cancer Society: Cancer Facts and Figures 2016. Atlanta, Ga: American Cancer Society, 2016. Available online. Last accessed May 19, 2016.

2. Altekruse SF, Kosary CL, Krapcho M, et al.: SEER Cancer Statistics Review, 1975-2007. Bethesda, Md: National Cancer Institute, 2010. Also available online. Last accessed February 2, 2016.

3. Johnson A, Shekhdar J: Breast cancer incidence: what do the figures mean? J Eval Clin Pract 11 (1): 27-31, 2005.[PUBMED Abstract]

4. Haas JS, Kaplan CP, Gerstenberger EP, et al.: Changes in the use of postmenopausal hormone therapy after the publication of clinical trial results. Ann Intern Med 140 (3): 184-8, 2004.[PUBMED Abstract]

5. Colditz GA, Rosner BA, Speizer FE: Risk factors for breast cancer according to family history of breast cancer. For the Nurses' Health Study Research Group. J Natl Cancer Inst 88 (6): 365-71, 1996.[PUBMED Abstract]

6. Colditz GA, Kaphingst KA, Hankinson SE, et al.: Family history and risk of breast cancer: nurses' health study. Breast Cancer Res Treat 133 (3): 1097-104, 2012.[PUBMED Abstract]

7. Malone KE, Daling JR, Doody DR, et al.: Family history of breast cancer in relation to tumor characteristics and mortality in a population-based study of young women with invasive breast cancer. Cancer Epidemiol Biomarkers Prev 20 (12): 2560-71, 2011.[PUBMED Abstract]

8. Cybulski C, Wokołorczyk D, Jakubowska A, et al.: Risk of breast cancer in women with a CHEK2 mutation with and without a family history of breast cancer. J Clin Oncol 29 (28): 3747-52, 2011.[PUBMED Abstract]

9. Goodwin PJ, Phillips KA, West DW, et al.: Breast cancer prognosis in BRCA1 and BRCA2 mutation carriers: an International Prospective Breast Cancer Family Registry population-based cohort study. J Clin Oncol 30 (1): 19-26, 2012.[PUBMED Abstract]

10. Mavaddat N, Barrowdale D, Andrulis IL, et al.: Pathology of breast and ovarian cancers among BRCA1 and BRCA2 mutation carriers: results from the Consortium of Investigators of Modifiers of BRCA1/2 (CIMBA). Cancer Epidemiol Biomarkers Prev 21 (1): 134-47, 2012.[PUBMED Abstract]

11. Miki Y, Swensen J, Shattuck-Eidens D, et al.: A strong candidate for the breast and ovarian cancer susceptibility gene BRCA1. Science 266 (5182): 66-71, 1994.[PUBMED Abstract]

12. Futreal PA, Liu Q, Shattuck-Eidens D, et al.: BRCA1 mutations in primary breast and ovarian carcinomas. Science 266 (5182): 120-2, 1994.[PUBMED Abstract]

13. Wooster R, Neuhausen SL, Mangion J, et al.: Localization of a breast cancer susceptibility gene, BRCA2, to chromosome 13q12-13. Science 265 (5181): 2088-90, 1994.[PUBMED Abstract]

14. Hamajima N, Hirose K, Tajima K, et al.: Alcohol, tobacco and breast cancer--collaborative reanalysis of individual data from 53 epidemiological studies, including 58,515 women with breast cancer and 95,067 women without the disease. Br J Cancer 87 (11): 1234-45, 2002.[PUBMED Abstract]

15. Boyd NF, Martin LJ, Rommens JM, et al.: Mammographic density: a heritable risk factor for breast cancer. Methods Mol Biol 472: 343-60, 2009.[PUBMED Abstract]

16. McCormack VA, dos Santos Silva I: Breast density and parenchymal patterns as markers of breast cancer risk: a meta-analysis. Cancer Epidemiol Biomarkers Prev 15 (6): 1159-69, 2006.[PUBMED Abstract]

17. Key TJ, Appleby PN, Reeves GK, et al.: Circulating sex hormones and breast cancer risk factors in postmenopausal women: reanalysis of 13 studies. Br J Cancer 105 (5): 709-22, 2011.[PUBMED Abstract]

18. Kaaks R, Rinaldi S, Key TJ, et al.: Postmenopausal serum androgens, oestrogens and breast cancer risk: the European prospective investigation into cancer and nutrition. Endocr Relat Cancer 12 (4): 1071-82, 2005.[PUBMED Abstract]

19. Kaaks R, Berrino F, Key T, et al.: Serum sex steroids in premenopausal women and breast cancer risk within the European Prospective Investigation into Cancer and Nutrition (EPIC). J Natl Cancer Inst 97 (10): 755-65, 2005.[PUBMED Abstract]

20. Endogenous Hormones and Breast Cancer Collaborative Group: Endogenous sex hormones and breast cancer in postmenopausal women: reanalysis of nine prospective studies. J Natl Cancer Inst 94 (8): 606-16, 2002.[PUBMED Abstract]

21. Collaborative Group on Hormonal Factors in Breast Cancer: Menarche, menopause, and breast cancer risk: individual participant meta-analysis, including 118 964 women with breast cancer from 117 epidemiological studies. Lancet Oncol 13 (11): 1141-51, 2012.[PUBMED Abstract]

22. Ritte R, Lukanova A, Tjønneland A, et al.: Height, age at menarche and risk of hormone receptor-positive and -negative breast cancer: a cohort study. Int J Cancer 132 (11): 2619-29, 2013.[PUBMED Abstract]

23. Kampert JB, Whittemore AS, Paffenbarger RS Jr: Combined effect of childbearing, menstrual events, and body size on age-specific breast cancer risk. Am J Epidemiol 128 (5): 962-79, 1988.[PUBMED Abstract]

24. Breast cancer and hormone replacement therapy: collaborative reanalysis of data from 51 epidemiological studies of 52,705 women with breast cancer and 108,411 women without breast cancer. Collaborative Group on Hormonal Factors in Breast Cancer. Lancet 350 (9084): 1047-59, 1997.[PUBMED Abstract]

25. 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): 321-33, 2002.[PUBMED Abstract]

26. Chlebowski RT, Anderson GL, Gass M, et al.: Estrogen plus progestin and breast cancer incidence and mortality in postmenopausal women. JAMA 304 (15): 1684-92, 2010.[PUBMED Abstract]

27. Chlebowski RT, Hendrix SL, Langer RD, et al.: Influence of estrogen plus progestin on breast cancer and mammography in healthy postmenopausal women: the Women's Health Initiative Randomized Trial. JAMA 289 (24): 3243-53, 2003.[PUBMED Abstract]

28. Chlebowski RT, Manson JE, Anderson GL, et al.: Estrogen plus progestin and breast cancer incidence and mortality in the Women's Health Initiative Observational Study. J Natl Cancer Inst 105 (8): 526-35, 2013.[PUBMED Abstract]

29. Wolin KY, Carson K, Colditz GA: Obesity and cancer. Oncologist 15 (6): 556-65, 2010.[PUBMED Abstract]

30. Morimoto LM, White E, Chen Z, et al.: Obesity, body size, and risk of postmenopausal breast cancer: the Women's Health Initiative (United States). Cancer Causes Control 13 (8): 741-51, 2002.[PUBMED Abstract]

31. Kotsopoulos J, Chen WY, Gates MA, et al.: Risk factors for ductal and lobular breast cancer: results from the nurses' health study. Breast Cancer Res 12 (6): R106, 2010.[PUBMED Abstract]

32. Goldacre MJ, Abisgold JD, Yeates DG, et al.: Benign breast disease and subsequent breast cancer: English record linkage studies. J Public Health (Oxf) 32 (4): 565-71, 2010.[PUBMED Abstract]

33. Kabat GC, Jones JG, Olson N, et al.: A multi-center prospective cohort study of benign breast disease and risk of subsequent breast cancer. Cancer Causes Control 21 (6): 821-8, 2010.[PUBMED Abstract]

34. Worsham MJ, Raju U, Lu M, et al.: Risk factors for breast cancer from benign breast disease in a diverse population. Breast Cancer Res Treat 118 (1): 1-7, 2009.[PUBMED Abstract]

35. Pearlman MD, Griffin JL: Benign breast disease. Obstet Gynecol 116 (3): 747-58, 2010.[PUBMED Abstract]

36. Vogel VG: Epidemiology, genetics, and risk evaluation of postmenopausal women at risk of breast cancer. Menopause 15 (4 Suppl): 782-9, 2008 Jul-Aug.[PUBMED Abstract]

37. Degnim AC, Visscher DW, Berman HK, et al.: Stratification of breast cancer risk in women with atypia: a Mayo cohort study. J Clin Oncol 25 (19): 2671-7, 2007.[PUBMED Abstract]

38. Worsham MJ, Abrams J, Raju U, et al.: Breast cancer incidence in a cohort of women with benign breast disease from a multiethnic, primary health care population. Breast J 13 (2): 115-21, 2007 Mar-Apr.[PUBMED Abstract]

39. Razzaghi H, Troester MA, Gierach GL, et al.: Mammographic density and breast cancer risk in White and African American Women. Breast Cancer Res Treat 135 (2): 571-80, 2012.[PUBMED Abstract]

40. Pfeiffer RM, Mitani A, Matsuno RK, et al.: Racial differences in breast cancer trends in the United States (2000-2004). J Natl Cancer Inst 100 (10): 751-2, 2008.[PUBMED Abstract]

41. Andrieu N, Easton DF, Chang-Claude J, et al.: Effect of chest X-rays on the risk of breast cancer among BRCA1 Breast Cancer Treatment–Health Professional Version (PDQ®)

1

General Information About Breast Cancer

This summary discusses primary epithelial breast cancers in women. The breast is rarely affected by other tumors such as lymphomas, sarcomas, or melanomas. Refer to the following PDQ summaries for more information on these cancer types:

Adult Hodgkin Lymphoma Treatment

Adult Soft Tissue Sarcoma Treatment

Melanoma Treatment

Breast cancer also affects men and children and may occur during pregnancy, although it is rare in these populations. Refer to the following PDQ summaries for more information:

Male Breast Cancer Treatment

Breast Cancer Treatment and Pregnancy

Unusual Cancers of Childhood Treatment

Incidence and Mortality

Estimated new cases and deaths from breast cancer (women only) in the United States in 2016:[1]

New cases: 246,660.

Deaths: 40,450.

Breast cancer is the most common noncutaneous cancer in U.S. women, with an estimated 61,000 cases of in situ disease, 246,660 cases of invasive disease, and 40,450 deaths expected in 2016[1]. Thus, fewer than one of six women diagnosed with breast cancer die of the disease. By comparison, it is estimated that about 72,160 American women will die of lung cancer in 2016[1]. Men account for 1% of breast cancer cases and breast cancer deaths (refer to the Special Populations section in the PDQ summary on Breast Cancer Screening for more information).

Widespread adoption of screening increases breast cancer incidence in a given population and changes the characteristics of cancers detected, with increased incidence of lower-risk cancers, premalignant lesions, and ductal carcinoma in situ (DCIS). (Refer to the Ductal Carcinoma In Situ section in the Breast Cancer Diagnosis and Pathology section in the PDQ summary on Breast Cancer Screening for more information.) Population studies from the United States [2] and the United Kingdom [3] demonstrate an increase in DCIS and invasive breast cancer incidence since the 1970s, attributable to the widespread adoption of both postmenopausal hormone therapy and screening mammography. In the last decade, women have refrained from using postmenopausal hormones, and breast cancer incidence has declined, but not to the levels seen before the widespread use of screening mammography[4].

Anatomy

Anatomy of the female breast. The nipple and areola are shown on the outside of the breast. The lymph nodes, lobes, lobules, ducts, and other parts of the inside of the breast are also shown.

Risk and Protective Factors

Increasing age is the most important risk factor for breast cancer[2]. Other risk factors for breast cancer include the following:

Family health history[5].

Major inheritance susceptibility[6][7][8].