Could modification of lifestyle factors prevent second primary breast cancers?

Modifiable factors have increasingly been associated with breast cancer. Studies have long suggested a link between modifiable factors, such as weight, physical activity, and alcohol use, and the risk of developing a primary breast cancer. Dozens of case-control and prospective cohort studies have demonstrated up to a two-fold increase in risk of breast cancer in overweight and obese postmenopausal women. Inactivity and regular consumption of alcohol have similarly been consistently shown to be associated with higher rates of primary breast cancer. Recent data also suggest that modifiable factors could impact breast cancer prognosis; observational data demonstrate that obesity and inactivity are associated with increased risk of cancer recurrence, while data from randomized trials suggest that dietary modification may decrease the risk of breast cancer recurrence, at least in some patient subsets. Much less is known regarding the relationship between modifiable factors and risk of a second primary breast cancer. A few recent reports have begun to evaluate the relationship between weight, alcohol intake, and smoking and the incidence of second primary breast cancers. In a prospective cohort of 10,953 women with newly diagnosed breast cancer, Trentham-Dietz et al found that women with a greater body mass index and those who had gained a significant amount of weight in adulthood were at increased risk of second primary breast cancer (P .003 and P .02, respectively), but did not find an increase risk of second breast cancer based on alcohol use or smoking history. Li et al reported an increased risk of second breast cancer in obese women diagnosed with breast cancer before age 45 (odds ratio [OR], 2.6; 95% CI, 1.1 to 5.9), but did not see any relationship between alcohol intake and risk of contralateral breast cancer in this group. Digham et al reported an increased risk of second breast cancers associated with obesity in both women with estrogen receptor (ER)–positive cancers assigned to tamoxifen or placebo in the National Surgical Adjuvant Breast and Bowel Program B-14 study, and in women with ER-negative tumors in a variety of National Surgical Adjuvant Breast and Bowel Program trials. Finally, Knight et al found a marginally significant relationship between ever drinking and risk of second primary breast cancer (risk ratio, 1.3; 95% CI, 1.0 to 1.6) in a case control study of 708 women with asynchronous contralateral breast cancers, as compared with 1,399 women with unilateral breast cancer. No relationship between smoking and risk of second breast cancer was seen. In this issue, Li et al report an increased risk of second primary breast cancers associated with obesity, regular alcohol use and smoking. The authors compared weight and alcohol and smoking behaviors in 365 cases diagnosed with an ER-positive breast cancer and a subsequent contralateral breast cancer, and in 726 controls diagnosed only with a primary ER-positive breast cancer. Women who were overweight at the time of their first breast cancer diagnosis were 50% more likely to develop a second breast cancer as compared with women who had a body mass index lower than 25 kg/m (OR, 1.5; 95% CI, 1.0 to 2.1). Women who consumed more than seven drinks/ week after their first breast cancer diagnosis had a 70% increase in the risk of a contralateral breast cancer as compared with nondrinkers (OR, 1.9; 95% CI, 1.1 to 3.2), and women who smoked after breast cancer diagnosis had more than a two-fold increase in their risk of second breast cancer as compared with nonsmokers (OR, 2.2; 95% CI, 1.2 to 4.0). Alcohol use and smoking appeared to be synergistically associated with an increased risk of second breast cancer, with individuals who both smoked and drank 7 alcohol beverages per week having a seven-fold increase in risk as compared to individuals who did neither. Of note, control patients were significantly more likely to have been treated with hormonal therapy after their primary breast cancer (P .0001), and cases were numerically, but not statistically, more likely to have had a first-degree relative with breast cancer (29.5% v 25.5%; P .29). Other treatment and tumor characteristics were distributed similarly between cases and controls. So does this mean that women should be advised to lose weight and avoid alcohol and smoking after breast cancer diagnosis in order to reduce the risk of a second primary breast cancer? Excess weight and smoking are certainly associated with other adverse health outcomes, and the finding that obesity is associated with increased risk of second breast cancer is consistent with most other reports on this topic. Conversely, although regular alcohol intake has been linked to risk of primary breast cancer, moderate alcohol intake may actually have beneficial health effects, such as lowering the risk of heart disease. Given the inconsistencies regarding the relationship between moderate alcohol use and adverse outcomes in patients with breast cancer, it would be premature to counsel survivors to avoid all alcohol, based on current evidence. In addition, it is important to recognize that identification of relationships between potentially modifiable risk factors such as weight and alcohol use and risk of second primary breast cancers does not mean that modification of these factors after primary breast cancer diagnosis will reduce rates of second cancers. Although an exploratory analysis by Li et al showed that current smoking appeared to confer a greater risk of second breast cancer than past smoking, many studies suggest that risk of breast cancer may be more strongly affected by exposures earlier in life. There is almost no data JOURNAL OF CLINICAL ONCOLOGY E D I T O R I A L