Kathleen E. Malone

Frequency of BRCA1/BRCA2 mutations in a population-based sample of young breast carcinoma cases.

There is a clear and growing need for data regarding BRCA1 and BRCA2 mutation frequencies among breast carcinoma cases not specifically ascertained on the basis of extreme family history profiles. Toward this end, the authors previously reported results with regard to BRCA1 in breast carcinoma patients drawn from a population‐based study. In the current study the authors present new findings concerning BRCA2 mutation frequency in this same population, as well as summary data regarding the combined contribution of these two genes.

Perinatal factors and risk of breast cancer

A high level of endogenous estrogen in utero has been hypothesized to he a possible risk factor for breast cancer. We used information from two population-hosed case-control studies to investigate the relation between perinatal factors and risk of invasive breast cancer among women age 21–45 years (746 cases, 960 controls) and women age 50–64 years (401 cases, 439 controls). Breast cancer cases were ascertained through a population-based cancer registry, and controls were selected by random digit dialing. After adjustment for age, menopausal status, and maternal smoking, the birthweight-breast cancer association in women age 21–45 years followed a J-shaped curve, with women whose birthweight was less than 2,500 gm [odds ratio (OR) = 1.3; 95.4, confidence interval (CI) = 09–2.01 and 4,000 gm or more (OR = 1.7; 95% CI = 1.1–2.5) at increased risk. Women age 50–64 years who were 4,000 gm or more at birth appeared to be at slightly reduced risk of breast cancer (OR = 0.6; 95% CI = 0.3–1.1). With the exception of maternal smirking, there was little effect of other perinatal factors on breast cancer risk in either group. These results support the hypothesized association between intrauterine estrogen exposure and subsequent risk of breast cancer.

Relation of regimens of combined hormone replacement therapy to lobular, ductal, and other histologic types of breast carcinoma†

The incidence of invasive lobular carcinoma has been increasing among postmenopausal women in some parts of the United States. Part of this may be due to changes in classification over time. However, the use of combined (estrogen and progestin) hormone replacement therapy (CHRT) also has increased during the last decade and may account in part for the increase in invasive lobular breast carcinoma.

Childbearing and survival after breast carcinoma in young women

Many young patients with breast carcinoma have not started, or completed, their desired families. How childbearing after a diagnosis of breast carcinoma affects survival is of importance to these women and their families. The authors measured relative mortality among young patients with breast carcinoma with and without births occurring after diagnosis.

The association between 3-hydroxy-3-methylglutaryl conenzyme a inhibitor use and breast carcinoma risk among postmenopausal women: A case-control study

Statin use has increased dramatically in the U.S. in the past decade. Animal and mechanistic studies suggested that statins may have an inhibitory effect on cancer proliferation, including breast carcinoma. However, statins have been found to be carcinogenic in rodents and one clinical trial found an excess of breast carcinoma cases in the treatment group.

Reproductive and hormonal risk factors for postmenopausal luminal, HER-2-overexpressing, and triple-negative breast cancer

Molecular profiling studies have identified subtypes of breast cancer that can be approximately classified by estrogen receptor (ER), progesterone receptor (PR), and HER‐2/neu (HER‐2) expression. These molecular subtypes are prognostically significant, but to the authors knowledge, differences in their etiologic profiles have not been established. Reproductive factors may plausibly be differentially correlated with the risk of different breast cancer subtypes because these factors are presumed to impact exposure to endogenous sex hormones.

Relation between use of antihypertensive medications and risk of breast carcinoma among women ages 65-79 years

Limited data are available regarding the incidence of breast carcinoma among users of relatively recently introduced forms of antihypertensive therapy. Although it has been suggested that women who have taken calcium channel blockers (CCBs) have an increased risk and that women who have taken angiotensin‐I‐converting enzyme (ACE) inhibitors have a decreased risk, currently, no conclusions can be drawn.

Body Size and Risk of Luminal, HER2-Overexpressing, and Triple-Negative Breast Cancer in Postmenopausal Women

Although the clinical relevance of molecular subtypes of breast cancer has been documented, little is known about risk factors for different tumor subtypes, especially the HER2-overexpressing and the triple-negative subtypes that have poor prognoses. Obesity may be differentially related to the risk of different subtypes given the various potential mechanisms underlying its association with breast cancer. We pooled two population-based case-control studies of postmenopausal breast cancer for an analysis, including 1,447 controls and 1,008 luminal (hormone receptor positive), 39 HER2-overexpressing (hormone receptor negative, HER2 positive), and 77 triple-negative (hormone receptor and HER2 negative) cases. Associations between anthropometric factors and the risk of different breast cancer subtypes were evaluated using polytomous logistic regression. Among women not currently using menopausal hormone therapy, body mass index (BMI) and weight were associated with the risk of luminal tumors [odds ratio (OR) comparing highest versus lowest quartiles, 1.7; 95% confidence interval (95% CI), 1.2-2.4 and OR, 1.7; 95% CI, 1.2-2.4, respectively] and suggestively associated with risk of triple-negative tumors (OR, 2.7; 95% CI, 1.0-7.5 and OR, 5.1; 95% CI, 1.1-23.0, respectively). Neither BMI nor weight was associated with the risk of any tumor subtype among hormone therapy users. The positive relationship between BMI and luminal tumors among postmenopausal women not using hormone therapy is well characterized in the literature. Although our sample size was limited, body size may also be related to the risk of postmenopausal triple-negative breast cancer among nonusers of hormone therapy. Given the expanding obesity epidemic, the widespread cessation of hormone therapy use, and the poor prognosis of triple-negative tumors, this novel finding merits confirmation. (Cancer Epidemiol Biomarkers Prev 2008;17(8):2078–86)

Breast Cancer Risk and Hormone Receptor Status in Older Women by Parity, Age of First Birth, and Breastfeeding: A Case-Control Study

Background: Early age at first birth and multiparity reduce the risk of estrogen receptor-progesterone receptor (ERPR)–positive breast cancer, whereas breastfeeding reduces the risk of both ERPR-positive and ERPR-negative cancers. Methods: We used multivariable logistic regression analysis to investigate whether age at first birth (<25 or ≥25 years) and breastfeeding (ever/never) modify the long-term effect of parity on risk of ERPR-positive and ERPR-negative cancer using 1,457 incident breast cancer cases and 1,455 controls ages ≥55 years who participated in the Womens Contraceptive and Reproductive Experiences Study. Results: Women who gave birth before age 25 years had a 36% reduced risk of breast cancer compared with nulligravida that was not observed for women who started their families at an older age (Pheterogeneity = 0.0007). This protective effect was restricted to ERPR-positive breast cancer (Pheterogeneity = 0.004). Late age at first birth increased the risk of ERPR-negative cancers. Additional births reduced the risk of ERPR-positive cancers among women with an early first birth (Ptrend = 0.0001) and among women who breastfed (Ptrend = 0.004) but not among older mothers or those who never breastfed. In women with a late first birth who never breastfed, multiparity was associated with increased risk of breast cancer. Conclusions: These findings suggest that the effect of parity on a womans long-term risk of breast cancer is modified by age at first full-term pregnancy and possibly by breastfeeding. (Cancer Epidemiol Biomarkers Prev 2008;17(7):1723–30)

Alcohol consumption and breast cancer risk among women under age 45 years

In a population‐based case‐control study of women younger than 45 years of age, we obtained a detailed lifetime history of alcohol use to evaluate the effects of drinking during different periods of life in relation to breast cancer risk. This analysis focused on interviews obtained from 1,645 cases and 1,497 controls. Breast cancer risk was not influenced by drinking during the teenage years or early adulthood. Contemporary drinking (that is, average intake during the recent 5‐year interval) was directly associated with risk, but the adverse effect of recent drinking was restricted to women who consumed ≥14 drinks per week [relative risk (RR) = 1.7; 95% confidence interval (CI) = 1.2–2.5]. The effect of alcohol was most pronounced among women with advanced disease. Compared with nondrinkers, the risk estimate associated with recent consumption of ≥14 drinks per week was 2.4 (95% CI = 1.6–3.8) for women with regional/distant disease. Our data add support to the accumulating evidence that alcohol consumption is associated with increased risk of breast cancer and further indicate that alcohol acts at a late stage in breast carcinogenesis.