Study: Higher BMI associated with reduced breast Ca risk in premenopausal women

According to recently published findings in JAMA Oncology, higher body mass index (BMI) is linked to lower risk of breast cancer in premenopausal women. While obesity has been shown to have a strong correlation with an increased risk of breast cancer in postmenopausal women, the results from this large-scale, multicenter analysis show that the inverse may actually be true for younger women.

The researchers collected data from 19 prospective cohorts in North America (n=9), Europe (n=7), Asia (n=2), and Australia (n=1). Participants in these cohorts were recruited from January 1, 1963 through December 31, 2013. Data from each study were standardized to a common template for 1 to 16 questionnaire rounds per study. The researchers also took self-reported or measured information on current weight and height to construct BMI within the age ranges of 18 to 24, 25 to 34, 35 to 44, and 45 to 55. All of the breast cancers included in the study were diagnosed before menopause and the main analytic endpoint was invasive or in situ premenopausal breast cancer.

The analyses included 758,592 women (median age, 40.6 years; interquartile range, 35.2-45.5 years). Among these women, 13,082 in situ or invasive breast cancer cases occurred during 7.2 million premenopausal years of follow-up (median, 9.3 years; interquartile range, 4.9-13.5 years). Depending on age, 88.9% to 99.6% of weights were self-reported. Weight at ages 18 to 24 was retrospectively reported for 96.9% of women, but that was the case for fewer than 10% of women who were older. The researchers noted that obesity was more common in women who were aged 45 and older (11.1%), nulliparous (12.4%), had a family history of breast cancer (12.8%), had an early menarche (17.0%), or were black (26.8%). 

The researchers found a linear association between increasing BMI and decreasing risk of breast cancer, but there appeared to be a leveling of risk for underweight women (BMI < 18.5) for some ages and tumor types when compared to women in the normal weight range (BMI 18.5-24.9). As a result, the authors restricted the linear modeling of BMI to values ≥ 18.5. Hazard ratios for breast cancer decreased as BMI increased, more so with younger than older women. The researchers saw a risk reduction of 23% per each 5 kg/m²increase in BMI (HR, 0.77; 95% CI, 0.73-0.80) at ages 18 to 24 and 12% (HR, 0.88; 95% CI, 0.86-0.91) for BMI increases at 45 to 54 years. Between the highest and lowest BMI categories (BMI ≥ 35.0 vs < 17.0) at ages 18 to 24 years, the risk gradient was 4.2-fold (HR, 0.24; 95% CI, 0.14-0.40). Even within the normal range for BMI, significant differences in relative risk were observed (23.0-24.9 vs 18.5-22.9: HR, 0.80; 95% CI,0.75-0.86). HRs for BMI at 18 to 24 years stayed significantly significant even after additional adjustment for the woman’s most recent BMI measurement (HR per 5kg/m²increase, 0.80; 95% CI, 0.76-0.84).

Among the 2138 incident cases of in situ breast cancer, associations with risk per 5 kg/m²difference in BMI were significantly larger (HR, 0.76; 95% CI, 0.69-0.85) compared to the 10,836 incident cases of invasive breast cancer (HR, 0.88; 95% CI, 0.84-0.92) (P = .02 for interaction), at ages 25 to 34. At ages 35 to 44 years, difference in associations were also found for in situ (HR, 0.81; 95% CI 0.76-0.86) and invasive breast cancer (HR, 0.88; 95% CI 0.86-0.90) (P = .01).

The authors noted a few strengths and limitations to their study. Among the noted strengths were the large number of cases and the precise estimates of relative risk they provided. Some limitations were use of BMI since women can have different body fat distributions and levels but still have the same BMI. Participants were also asked to retrospectively come up with their height and weight at age 18. In addition, one of the included studies asked participants to self-report their current weight and overweight women tend to underreport while underweight women tend to overreport. Ultimately, the researchers believe the results of their study suggest that increased BMI has a more significant association with reduced breast cancer risk in premenopausal women than previous analyses. However, more research is necessary to better understand the biological mechanism causing this association.

Automated screening links breast density to risk of breast Ca

Women with denser breast tissue have higher recall and biopsy rates and increased odds of screen-detected and interval breast cancer, according to a study by Norwegian investigators. Published in Radiology, the results support use of automated volumetric breast density (VBD) measurements as a future standard for ensuring objective breast density classification in breast cancer screening. 

The researchers used data from the Cancer Registry of Norway, which was started in 1996 and reflects outcomes of biennial mammography offered to approximately 600,000 Norwegian women aged 50 to 69. For this study, the researchers looked at outcomes in 107,949 women with mean age at time of screening of 58.3 ± 5.7 years. 

On average, the participants underwent 2.8 screening examinations during the study period (January 1, 2007 to December 31, 2015), accounting for 307,015 total examinations. Individual breast cancer risk factors were obtained through a questionnaire, and information was available from 62% of the women (66817 of 107,949). Variables considered in the study included weight, height, use of hormonal therapy, number of pregnancies lasting greater than 6 months, and family history of breast cancer (first- and second-degree). 

The researchers used software to classify breast density on a four-category scale. Examinations with VBD ≤ 4.5% were classified as density of grade 1, those with 4.5%-7.49% were classified as grade 2, those with 7.5%-15.49 were classified as grade 3, and those with VBD ≥ 15.5 were classified as grade 4. In the study, grades 1 and 2 combined were considered indicative of “non-dense breasts” (VBD < 7.5%) and grades 3 and 4 combined considered “dense breasts” (VBD ≥ 7.5%).

Of the 307,015 screenings, 14% were the women’s first examination in BreastScreen Norway, 82% were screenings less than 752 days since last examination, and 4% were screenings greater ≥ 752 days since last examination). VBD measurements ranged from 1% to 52% and 72% (219,994) of the examinations were classified as non-dense and 28% (87021) were classified as dense. The recall rate was 2.7% (5882 of 219,994) for screening examinations of women with non-dense breasts and 3.6% (3101 of 87021) for women with dense breasts. 

In non-dense breasts, the rate of needle biopsy resulting from abnormal screening was 1.1% (2359 of 219,994) versus 1.4% (1209 of 87021) for women with dense breasts. The researchers observed a lower rate of breast cancer in women with non-dense breasts compared to women with dense breasts: 5.5 (1201 of 219,994) versus 6.7 (581 of 87021) per 1000 examinations for screen-detected breast cancer. In examinations for interval breast cancer, rates were 1.2 (199 of 165324) vs 2.8 (185 of 66674) per 1000 examinations. In women with screen-detected breast cancer, a smaller proportion of those with non-dense breasts than with dense breasts had ductal carcinoma in situ (20% vs 26%, respectively). Mean tumor diameter also was smaller in the women with non-dense breasts (15.1 mm vs 16.6 mm, respectively; P= .009). The researchers found that age, body mass index, use of hormonal therapy, number of pregnancy and breast cancer family history were significantly associated with volumetric density categories. 

For screening examinations of women with dense versus non-dense breasts, the adjusted odds of a screen-detected breast cancer were 1.37 times higher (95% CI: 1.19-1.59) in women with dense breasts compared to non-dense. Compared to women with non-dense breasts, women with dense breasts had 2.93 times higher (95% CI: 2.16-3.97) odds of an interval breast cancer. The subset of the study cohort with the highest predicted number of screen-detected breast cancers were women at least 65 years with very high breast density (30% or higher) with approximately 13 detections per 1000 screening examinations. Women with very low breast density (< 4%) had the lowest predicted number of cases of screen-detected breast cancer (< 5 per 1000 screening examinations).

The authors believe their findings support previous research regarding breast density and breast cancer risk. However, they believe that using automated volumetric mammographic density, they were able to identify higher rates of recall and biopsy and higher odds of screen-detected and interval breast cancer. They suggest that automated volumetric mammographic density can be used to help develop better screening protocols for women with dense breasts and help standardize density measurements.