It has been observed that in early BC, a higher BMI is associated with poorer prognosis. Further, it has been postulated that aromatase inhibitor (AI) therapy may confer less protection in those who are obese compared with those who are not obese.

Aromatase is expressed in adipose tissue and is involved in the conversion of androgen into estrogen. Obesity may render AIs less effective in suppressing estradiol production, possibly by affecting drug metabolism and distribution. The ATAC (Arimidex, Tamoxifen, Alone or in Combination) trial suggested that the efficacy of AI therapy is dependent upon body weight, with more recurrences occurring in the patients who are obese. However, questions remain as other studies have found contrary results.

Investigators conducted a cohort study utilizing data from the Danish Breast Cancer Group Clinical Database (DBCGCD), Danish Civil Registration System, Danish National Patient Registry, and the Danish Anesthesia Database to examine the association between BMI with BC recurrence in patient treated with adjuvant AIs. The DBCGCD includes data on BC occurrence in >95% of the population in Denmark since 1977.

The study population included all postmenopausal women with a primary diagnosis of stage I to III hormone-receptor positive BC who were enrolled in the DBCGCD between January 1, 1998, and December 31, 2016. Obesity was defined as a BMI of 30.0-34.9, a BMI of >35 was considered severe obesity, and a BMI of 25.0-29.9 was deemed overweight; a BMI of 18.5-24.9 was considered a healthy weight.

The study end point was BC recurrence (i.e., the time from 6 months after the date of BC surgery) until the earliest occurrence of any BC recurrence recorded. Follow up started 6 months after BC surgery and was continued for up to 10 years or to September 25, 2018. Data were censored at the first occurrence of an event, which included BC recurrence, contralateral BC, new primary malignancy, death, or leaving the area.

The study included 13,230 postmenopausal women with primary, early-stage hormone-receptor-positive (HR+) BC (mean age at diagnosis: 64.4 years). The median follow-up period was 6.2 years.

At the time of BC diagnosis, 14.4% of patient were obese, 6.5% had severe obesity, and almost one-third (32.5%) were overweight. Patients who were obese or severely obese tended to be younger than those with a healthy weight or who were overweight at the time of diagnosis. Those who were obese, severely obese, or overweight had more comorbidities at diagnosis, tumors with a higher histological grade, more lymph node involvement, had larger tumors, more often had breast-conserving surgery, and were more likely to be treated with adjuvant chemotherapy and/or radiotherapy compared with patients who were normal weight.

Obesity was associated with an 18% increased risk of recurrence (adjusted hazard ratios [AHR] = 1.18; 95% CI, 1.01-1.37), whereas severe obesity was associated with a 32% increase in the risk of BC recurrence (AHR = 1.32; 95% CI, 1.08-1.62). Whereas being overweight was associated with a greater risk of BC recurrence than being normal weight, this finding did not reach statistical significance. Using restricted cubic splines, the researchers found that the risk of BC recurrence started increasing at a BMI of 25.0 or greater.

When contralateral BC, new primary malignancies, or death were considered, only the severely obese group showed a statistically significant 44% increase in recurrence compared with those with a healthy weight (AHR = 1.44; 95% CI, 1.17-1.77).

Pharmacists can play a major role in improving public health by encouraging weight loss and promoting healthy lifestyles in obese or severely obese patients with BC. The interventions may help mitigate the risk of recurrence in postmenopausal women who have an excessive BMI.

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