Breast cancer screening with mammography

The currently recommended method for reducing breast cancer mortality is through a clinical breast examination and mammogram. The American Cancer Society recommends that these begin at age 40 for women at average risk [13].

Mortality reduction associated with screening mammography

Regular screening with mammography has been consistently shown in randomized controlled trials to provide long-term reduction in breast cancer mortality [13]. In order to achieve a 30% reduction in breast cancer mortality, 80% of women aged 50 to 70 should comply with these guidelines. However, compliance with screening guidelines is often inadequate to achieve this goal. This is particularly the case among women of lower socioeconomic levels and among ethnic minorities [14].

Problems with mammography and barriers to compliance with screening guidelines

Radiation exposure with mammography

Concern over radiation from mammography represents one important barrier to compliance with screening recommendations [14-16]. This concern is especially relevant for women below the age of 50, where "the balance between the number of breast cancer deaths prevented by screening compared with the number induced by radiation seems less favourable" (p. 81) [17].

The female breast is a radiosensitive organ. As mentioned earlier in this chapter, exposure to ionizing radiation is consistently associated with an increased risk of breast cancer. The magnitude of risk is inversely related to age of exposure [1]. The very low energy X-rays used in screening mammography may be more harmful, per unit dose, than high-energy X-rays. Consequently, Brenner and colleagues [18] consider the estimated radiation risk for younger women as sufficient to warrant commencing routine screening 5-10 years later than currently recommended.

^ Increased radiosensitivity with hereditary risk of breast cancer Mutations in the BRCA genes or heterozygous AT status, result in impaired DNA repair mechanisms and heightened sensitivity to radiation [6]. At the same time, it is among these women with hereditary risk, for whom screening at an earlier age and at more frequent intervals than for women at average risk has been suggested as a possible option [13]. According to Kuni [19], among the "very radiosensitive subgroup: the women bearing a mutation of the gene BRCA 1 or BRCA 2 ... repeated X-ray use must be definitely avoided (p. 443)."

• Limitations in sensitivity of mammography

Rosé et al. [20] estimate that the overall false negative rate for mammography is about 10 to 15%. They note that up to 10% of breast cancers are not identified by mammography even when palpable. A false negative mammogram contributes to a delay in breast cancer diagnosis and results in poorer prognosis [21]. Moreover, limitations in sensitivity contribute to the perception that mammography is ineffective for the early detection of breast cancer, and may, consequently, lower compliance with screening guidelines [22].

— Mammographically dense breasts

Although mammography is very sensitive for detecting breast cancer in fatty breast tissue, detection of malignant lesions (unless calcified) by mammography is very difficult in dense breasts [23].

Dense breasts are commonly seen in younger women. This is another reason why early mammography screening for women at high risk can be problematic.

Mammographically dense breasts are also associated with use of combined HRT and are considered a marker for increased breast cancer risk among women after menopause [24].

— Non-calcified lesions

Since breast cancer is a heterogeneous disease, the sensitivity of mammography varies in relation to the histopathologic subtype. While calcifications are relatively easy to see, these are present in only a minority of histologically-verified breast cancers, with the rest being non-calcified stellate and circular masses that are often much harder to perceive [25].

• Low specificity of mammography

Khalkhali and Itti [26] cite estimates of the positive predictive value of mammography as low as (15-30) %. Abnormal screening mammography may be followed up with compression or magnified views, and ultrasound can help determine whether the lesion is cystic or solid. Biopsy is recommended for breast lesions estimated to have > 3% risk of cancer [2].

Up to 80 to 90% of breast biopsies show benign findings, with the vast majority being due to fibrocystic disease (small fluid-filled cysts and fibrous hyperplasia). As noted in Section 16.1, benign breast disease is associated with an increased risk of breast cancer [2]. Biopsies of benign lesions are associated with considerable morbidity, including: — Anxiety.

The fear engendered by a false positive mammogram may lead to decreased compliance with screening guidelines, which can result in later-stage diagnosis of breast cancer and increased mortality [22].

^ Difficulties in subsequent mammographies after biopsy

Once a breast biopsy has been performed, subsequent mammographic evaluation in the region of the scarred tissue is rendered more difficult [21].

Innovations in mammography & other X-ray based diagnostic methods

Currently, screen-film mammography (SFM) is the gold standard for breast cancer screening. A number of promising innovations in mammography and other X-ray based methods for diagnosing breast cancer are on the horizon. Full-field digital mammography (FFDM) was recently approved by the U.S. Food and Drug Administration for breast cancer screening, and has shown improved specificity, i.e. significantly lower recall rate and lower biopsy rate compared to SFM. However, FFDM has an insignificantly lower sensitivity than SFM [13]. It should also be recalled that all these mammography-based techniques would still entail exposure to ionizing radiation.

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