Dense breast tissue in patients with breast cancer nearly doubles the risk for disease developing in the contralateral breast, according to the results of a study recently published in Cancer.
After evaluating more than 200 patients with breast cancer treated at The University of Texas MD Anderson Cancer Center in Houston and more than 400 matched controls, the researchers reported that “the odds of developing contralateral breast cancer were found to be significantly higher for patients with dense breasts (odds ratio [OR], 1.80; 95% confidence interval, 1.22-2.64 [P <.01]) than for those with nondense breasts.”
Women with dense breasts on mammography had previously been found to have a 2-fold increased risk for developing primary breast cancer. The new study is among the first to find the association between breast density and contralateral breast cancer.
An ongoing challenge for clinicians in the management of breast cancer, especially as they make surgical decisions, is trying to counsel women appropriately on their risk for developing contralateral breast cancer.
In a statement prepared by MD Anderson Cancer Center, Isabelle Bedrosian, MD, Associate Professor of Breast Surgical Oncology and a coinvestigator of the study, said, “We know there are a number of well-established influences for developing both primary and secondary breast cancers, such as BRCA mutations, family history, and the tumor’s estrogen receptor status.”
She went on to note that the estimated 10-year risk for women with breast cancer developing contralateral breast cancer ranges from 2% to 40%. The wide range is due in large part to the variability of risk factors across the patient population.
For the retrospective, case-controlled study, the researchers identified 680 patients with stage I, II, and III breast cancer who were treated between 1997 and 2012. Patients with the BRCA mutation were excluded from the study, given their known increased risk for developing contralateral breast cancer.
The cases constituted women with an additional diagnosis of metachronous contralateral breast cancer, defined as breast cancer in the opposite breast diagnosed more than 6 months after the initial diagnosis. Patients who had not developed contralateral breast cancer were designated as controls. Cases and controls were matched on a 1:2 ratio based on a number of factors, including age, year of diagnosis, and hormone receptor status.
There were 229 cases and 451 controls. Each patient’s breast density was categorized by mammogram reading, assessed at the time of first diagnosis, as nondense (American College of Radiology breast categories of fatty or scattered density) or dense (American College of Radiology categories of heterogeneously dense or extremely dense).
Approximately 39.3% of the cases were classified as having nondense breast tissue and 60.7% as having dense breast tissue, compared with 48.3% and 51.7%, respectively, in the controls.
The majority (86%) of cases and controls had stage I or II disease. Controls were slightly more likely to have invasive ductal disease compared with cases (82.5% vs 76%, respectively). Cases were less likely to have received chemotherapy (55.5% vs 68.1%) or endocrine therapy (66.8% vs 78%). Cases were more likely to have undergone a mastectomy and were less likely to have received radiotherapy.
On multivariate analysis, the researchers found almost a 2-fold increased risk for developing contralateral disease in breast cancer survivors with dense breasts (OR, 1.80; P <.01).
Patients who received chemotherapy (OR, 0.50; P <.01) or endocrine therapy (OR, 0.14; P <.01) had an independently lower risk for developing metachronous contralateral breast cancer after adjustment in the multivariate model. This finding is consistent with other studies showing a 35% to 40% reduction in the risk for developing contralateral breast cancer in women first treated with chemotherapy or endocrine therapy compared with patients not receiving any treatment, the investigators noted.
Hormone receptor status of the contralateral breast cancers did not differ between the dense and nondense breast tissue groups.
Because the effect of breast density on cancer risk persists for at least 5 to 10 years after assessment, breast density at the time of primary breast cancer appears to be important, the researchers concluded.