Breast Cancer Diagnosis and Pathology
Evaluation of Breast Symptoms
Women with breast symptoms are not candidates for screening because they require a diagnostic evaluation. During a 10-year period, 16% of 2,400 women aged 40 to 69 years sought medical attention for breast symptoms at their health maintenance organization. Women younger than 50 years were twice as likely to seek evaluation. Additional testing was performed in 66% of these women, including invasive procedures performed in 27%. Cancer was diagnosed in 6.2%, most often stage II or III. Of the breast symptoms prompting medical attention, a mass was most likely to lead to a cancer diagnosis (10.7%) and pain was least likely (1.8%) to do so.
Pathologic Diagnosis of Breast Cancer
Breast cancer is most often diagnosed by pathologic review of a fixed specimen of breast tissue. The breast tissue can be obtained from a symptomatic area or from an area identified by an imaging test. A palpable lesion can be biopsied with core needle biopsy or, less often, fine-needle aspiration biopsy or surgical excision; image guidance improves accuracy. Nonpalpable lesions can be sampled by core needle biopsy using stereotactic x-ray or ultrasound guidance or can be surgically excised after image-guided localization. In a retrospective study of 939 patients with 1,042 mammographically detected lesions who underwent core needle biopsy or surgical needle localization under x-ray guidance, sensitivity for malignancy was greater than 95% and the specificity was greater than 90%. Compared with surgical needle localization under x-ray guidance, core needle biopsy resulted in fewer surgical procedures for definitive treatment, with a higher likelihood of clear surgical margins at the initial excision.
Ductal Carcinoma In Situ
Ductal carcinoma in situ (DCIS) is a noninvasive condition that can evolve to invasive cancer, with variable frequency and time course. Some authors include DCIS with invasive breast cancer statistics, but others argue that the term be replaced by ductal intraepithelial neoplasia, similar to the terminology used for cervical and prostate precursor lesions, and that breast cancer statistics exclude these DCIS cases.
DCIS is most often diagnosed by mammography. In the United States, only 4,900 women were diagnosed with DCIS in 1983, compared with approximately 64,000 women who are expected to be diagnosed in 2013, when mammographic screening has been widely adopted.[3-5] The Canadian National Breast Screening Study-2 of women aged 50 to 59 years found a fourfold increase in DCIS cases in women screened by clinical breast examination (CBE) plus mammography compared with those screened by CBE alone, with no difference in breast cancer mortality. (Refer to the PDQ summary on Breast Cancer Treatment for more information.)
The natural history of DCIS is poorly understood because nearly all DCIS cases are treated. A single retrospective review of 11,760 breast biopsies performed between 1952 and 1968 identified 28 cases of DCIS,[7,8] which were detected by physical examination, biopsied without resection, and then followed for 30 years. Nine women developed invasive breast cancer and four women died of the disease. These findings are interesting but probably not relevant to women with screen-detected DCIS in an era of improved cancer care.
Development of breast cancer after treatment of DCIS depends on the characteristics of the lesion but also on the delivered treatment. One large randomized trial found that 13.4% of women treated by lumpectomy alone developed ipsilateral invasive breast cancer within 90 months, compared with 3.9% of those treated by lumpectomy and radiation. The best evidence indicates that most DCIS lesions will not evolve to invasive cancer and that those that do can still usually be managed successfully, even after that transition. Thus, the detection and treatment of nonpalpable DCIS often represents overdiagnosis and overtreatment.
Among women diagnosed with (and treated for) DCIS between 1984 and 1989, only 1.9% died of breast cancer within 10 years, which was a lower mortality rate than for the age-matched population at large. This favorable outcome may reflect the benign nature of the condition, the benefits of treatment, or the volunteer effect (women undergoing breast cancer screening are generally healthier than those who do not).
Attempts to define low-risk DCIS cases that can be managed with fewer therapies are important. One such effort analyzed a series of 706 DCIS patients who were monitored to develop the University of Southern California/Van Nuys Prognostic Scoring Index, which defines the risk of recurrent DCIS and invasive cancer among women with DCIS based on age, margin width, tumor size, and grade. The low-risk group, comprising a third of the cases, experienced only 1% DCIS recurrences and no invasive cancers, independent of the use of postoperative radiation therapy. The moderate- and high-risk groups had higher recurrence rates, and they benefited from postlumpectomy radiation therapy. Overall, only approximately 1% died of breast cancer. In a separate study, adjuvant tamoxifen therapy was shown to reduce the incidence of invasive breast cancer.
- Barton MB, Elmore JG, Fletcher SW: Breast symptoms among women enrolled in a health maintenance organization: frequency, evaluation, and outcome. Ann Intern Med 130 (8): 651-7, 1999. [PUBMED Abstract]
- White RR, Halperin TJ, Olson JA Jr, et al.: Impact of core-needle breast biopsy on the surgical management of mammographic abnormalities. Ann Surg 233 (6): 769-77, 2001. [PUBMED Abstract]
- Allegra CJ, Aberle DR, Ganschow P, et al.: National Institutes of Health State-of-the-Science Conference statement: Diagnosis and Management of Ductal Carcinoma In Situ September 22-24, 2009. J Natl Cancer Inst 102 (3): 161-9, 2010. [PUBMED Abstract]
- American Cancer Society: Cancer Facts and Figures 2013. Atlanta, Ga: American Cancer Society, 2013. Available online. Last accessed February 6, 2016.
- Virnig BA, Tuttle TM, Shamliyan T, et al.: Ductal carcinoma in situ of the breast: a systematic review of incidence, treatment, and outcomes. J Natl Cancer Inst 102 (3): 170-8, 2010. [PUBMED Abstract]
- Miller AB, To T, Baines CJ, et al.: Canadian National Breast Screening Study-2: 13-year results of a randomized trial in women aged 50-59 years. J Natl Cancer Inst 92 (18): 1490-9, 2000. [PUBMED Abstract]
- Page DL, Dupont WD, Rogers LW, et al.: Intraductal carcinoma of the breast: follow-up after biopsy only. Cancer 49 (4): 751-8, 1982. [PUBMED Abstract]
- Page DL, Dupont WD, Rogers LW, et al.: Continued local recurrence of carcinoma 15-25 years after a diagnosis of low grade ductal carcinoma in situ of the breast treated only by biopsy. Cancer 76 (7): 1197-200, 1995. [PUBMED Abstract]
- Fisher B, Dignam J, Wolmark N, et al.: Lumpectomy and radiation therapy for the treatment of intraductal breast cancer: findings from National Surgical Adjuvant Breast and Bowel Project B-17. J Clin Oncol 16 (2): 441-52, 1998. [PUBMED Abstract]
- Ernster VL, Barclay J, Kerlikowske K, et al.: Mortality among women with ductal carcinoma in situ of the breast in the population-based surveillance, epidemiology and end results program. Arch Intern Med 160 (7): 953-8, 2000. [PUBMED Abstract]
- Silverstein MJ: The University of Southern California/Van Nuys prognostic index for ductal carcinoma in situ of the breast. Am J Surg 186 (4): 337-43, 2003. [PUBMED Abstract]
- Fisher B, Dignam J, Wolmark N, et al.: Tamoxifen in treatment of intraductal breast cancer: National Surgical Adjuvant Breast and Bowel Project B-24 randomised controlled trial. Lancet 353 (9169): 1993-2000, 1999. [PUBMED Abstract]