[MOL] Destiny of Breast Cancer [01101]

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American Society of Clinical Oncology 35th Annual Meeting
Day 2 - May 16, 1999

Biology is Destiny in Breast Cancer: But Whose Destiny?

George W. Sledge, Jr, MD

Sir Francis Bacon wrote, "Nature to be commanded must be obeyed." This certainly holds true when it comes to tumor biology and breast cancer, as a number of presentations on Sunday attested.

Hereditary Breast Cancer: Bilateral Breast Cancer and Breast Conservation

Hereditary issues in breast cancer remain an important research theme. Although the broad outlines of hereditary breast cancer were set with the discovery of BRCA1 and BRCA2 earlier in the decade, many practical issues remain, some of which were examined at Sunday's sessions.

Robinson and colleagues^[1] from Israel examined the impact of BRCA1 and BRCA2 founder mutations on the risk of bilateral breast cancer. Ashkenazi Jews commonly have specific BRCA mutations (185delAG and 5382insC in BRCA1, 6174delT in BRCA2), which makes for somewhat easier screening in this population and leads to some interesting biologic analyses of specific mutations. In this study, the authors demonstrated that carrier rate for the founder mutations was significantly higher in women with bilateral breast cancer diagnosed at or before age 42.

Among patients with a positive family history and bilateral breast cancer, 45% carried 1 of the 3 target mutations. Of these, 86% (12/14) had 1 breast cancer diagnosed at or before the age of 42 years. These data suggest that bilateral breast cancer, commonly considered a risk factor for carrying a BRCA mutation, is only pertinent when the first cancer occurs at a young age. Whether these data are specific to this population, or generalizable to most or all BRCA1 and 2 carriers, remains to be seen.

Simmonds and colleagues^[2] posed a related question: Is breast conservation appropriate for women with hereditary breast cancer? Although not limiting their analysis to patients with BRCA1 or -2 mutations (all patients with a positive family history were included), these authors did tackle a clinically relevant question.

Comparing women with and without a positive family history of breast cancer, the researchers showed that there was no difference in local-regional relapse rates between the 2 groups. Contralateral breast cancers, however, were signficantly more common in women with a positive family history (32% vs 14%, P = .003), though this did not appear to alter long-term survival. Lumpectomy and radiation therapy represent a reasonable option for the patient with hereditary breast cancer.

Primary Chemotherapy: Can We Predict Who Will Benefit?

Primary chemotherapy (also known as preoperative chemotherapy) is increasingly used not only for locally advanced breast cancer but also for many patients wishing to improve their likelihood of breast preservation. But what's unclear is whether we can predict who will respond to therapy or who will survive. Two studies looked at this question.

Miller and colleagues^[3] from Aberdeen (UK) provided evidence that c-erbB-2 positivity and estrogen receptor (ER)-negativity predicted for pathologic complete response to chemotherapy. Generally known to predict for impaired prognosis in many settings, this may be a case for HER-2-positive and ER-negative tumors of "the last shall be first."

Chang and colleagues^[4] from MD Anderson Cancer Center examined the impact of body size on survival of women receiving preoperative chemotherapy. Obese premenopausal women had better survival than lean women, whereas obese postmenopausal women fared worse than their lean counterparts. Why might this be the case? In the postmenopausal setting, one might argue that higher circulating estrogen levels (due to greater peripheral aromatization of precursor steroids) might be to blame, though no evidence was provided to support this possibility.

References

Robinson E, Gershoni-Baruch R, Dagan E, Kepten I, Fried G. BRCA1 and BRCA2 founder mutations in patients with bilateral breast cancer [Abstract 2359]. American Society of Clinical Oncology 35th Annual Meeting, Atlanta, 1999.
Simmonds P, Eccles D, Goddard J, Evans G, Lalloo F, Royle G. Is breast conservation appropriate for women with hereditary breast cancer? [Abstract 2363]. American Society of Clinical Oncology 35th Annual Meeting, Atlanta, 1999.
Miller ID, Payne S, Walker LG, et al. Primary chemotherapy for breast cancer: biological predictors of pathological response [Abstract 2378]. American Society of Clinical Oncology 35th Annual Meeting, Atlanta, 1999.
Chang S, Alderfur J, Asmar L, Buzdar A. Inflammatory breast cancer: the influence of race, menopausal status and body size on survival [Abstract 2380].

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