Breast Density, Not BMI, Linked to Higher Cancer Risk in Lobular Carcinoma in Situ

Breast surgeon Dr. Melissa Pilewskie

Breast surgeon Dr. Melissa Pilewskie

Increased breast density was an additional risk factor for breast cancer in women with lobular carcinoma in situ (LCIS). However, body mass index (BMI) was not, according to our retrospective study published recently in the Annals of Surgical Oncology.

Among a group of 1,222 patients with LCIS, after a median follow-up of seven years, increased breast density was significantly associated with a higher risk of breast cancer (hazard ratio [HR] 2.42, 95 percent CI: 1/52 to 3.88). BMI had no impact on risk. (1)

We also found that the use of chemoprevention in patients with LCIS was associated with a significantly decreased risk of developing breast cancer (HR 0.49, 95 percent CI: 0.29 to 0.84). (1)

We also found that the use of chemoprevention in women with LCIS was associated with a significantly decreased risk of developing breast cancer.
Melissa L. Pilewskie Director, Strategic Planning and Research, RISE Program

Although LCIS is a relatively rare condition, diagnoses are rising. Women with LCIS have a significantly increased risk of developing either ductal carcinoma in situ (DCIS) or invasive breast cancer. We hope that our findings on the interplay of breast density and LCIS, and the protective benefits of chemoprevention, will assist physicians in counseling patients and performing personalized risk assessments.

Lobular Carcinoma in Situ

LCIS is found in about 0.5 to 5.3 percent of benign breast biopsies. The incidence has been increasing in recent years, from about 0.9 per 100,000 women in the late 1970s to 2.75 per 100,000 women in the early 2000s. (2), (3), (4), (5), (6), (7) Long-term follow-up studies report a seven to tenfold increased risk of developing cancer in either breast in women with LCIS, which amounts to about a 2 percent annual incidence of breast cancer in this patient population. (2), (8), (9), (10), (11), (12)

As the number of LCIS diagnoses rises, there is a growing need to identify and understand its related risk factors. Studies to date that have explored the additive risk of breast density in women with high-risk LCIS lesions have had mixed results. Furthermore, in the general population, the relationship between an increased BMI and breast cancer risk is complex and appears to differ by menopausal status. Obesity is an established risk factor for developing postmenopausal breast cancer. (13), (14) Characterizing the interplay between BMI and breast cancer risk has not been well studied in patients with high-risk LCIS lesions.

Study Design

We examined data from a prospectively maintained database of women with a diagnosis of LCIS who participated in a high-risk surveillance program at Memorial Sloan Kettering Cancer Center from 1988 to 2017. We excluded women with a BRCA mutation, a prior or concurrent cancer, pleomorphic LCIS, who were missing BMI or breast density values, or who had not returned for at least one follow-up visit. (1)

BMI was measured continuously and categorized according to the World Health Organization’s definition: Normal BMI is under 25; overweight is 25 to under 30; obese is 30 to under 35; and very obese is 35 and over. Breast density was measured by the mammographic Breast Imaging and Reporting and Data System (BIRADS) according to the imaging performed nearest in time to the LCIS diagnosis. Dense breast tissue is defined as BIRADS values C/D and nondense tissue as BIRADS values A/B. BIRADS values are defined as follows: A is fatty; B, scattered fibroglandular density; C, heterogenous or moderately dense; and D, extremely dense.

Screening by MRI was performed at the discretion of the physician and the patient. We published our experience with MRI screening in patients with LCIS previously. (15)

Risk-reduction strategies included chemoprevention and prophylactic mastectomy. Chemoprevention experience included the use of a selective estrogen receptor modulator or an aromatase inhibitor. We included women who had a bilateral prophylactic mastectomy in our analysis only up to the date of their surgery.

The primary outcome of our study was the development of DCIS or invasive breast cancer.

Study Results

Among 1,222 patients who met the inclusion criteria, the median BMI was 24 (interquartile range of 21.6 to 28.0), with 56 percent of patients in the normal weight category and nearly 80 percent of patients having dense breast tissue. Women with dense breast tissue were more likely to be under the age of 50 years, to be premenopausal, to have a lower BMI, and to have had more frequent MRI screening compared to those with nondense tissue. (1)

Sixty-three women in the higher breast density group had a prophylactic mastectomy, compared to only five in the lower breast density group. A total of 185 patients had used chemoprevention: 135 women with higher breast density and 50 women with lower breast density. (1)

At a median follow-up of seven years, 179 women (14.9 percent) had developed breast cancer: 122 had invasive breast cancer, and 58 had DCIS. In our multivariate analysis, women with higher breast density had a significantly increased risk of breast cancer. The HR was 2.42 for women with BIRADS C/D compared to BIRADS A/B (95 percent CI: 1.52 to 3.88). The ten-year cancer-free survival rate for patients with higher breast density was 0.81 (95 percent CI: 0.78 to 0.84) compared to 0.89 (95 percent CI: 0.85 to 0.94) for patients with lower breast density (p < 0.001). (1)

There was no significant difference in cancer-free probability by BMI category (p = 0.9). (1) Our exploratory analyses showed no significant interaction between BMI and menopausal status, BMI and breast density, BMI and chemoprevention use, or breast density and chemoprevention. (1)

Finally, the use of chemoprevention was associated with a significantly decreased hazard of developing breast cancer (HR 0.49, 95 percent CI: 0.29 to 0.84), irrespective of breast density. (1)

Advancing Breast Cancer Outcomes

At MSK, we are dedicated to improving outcomes for women at risk of developing breast cancer. Our Risk Assessment, Imaging, Surveillance, and Education Program (RISE) for people at increased risk of breast cancer is a comprehensive screening program that includes regular breast exams and imaging. Our goal is to identify any cancers that may arise as early as possible and to review options for risk reduction so that we can maximize patient outcomes. The RISE program is available at the Evelyn H. Lauder Breast Center in Manhattan, as well as at five regional MSK facilities.

We are currently conducting 73 breast cancer clinical trials, including a phase I study to see if endoxifen gel, a form of tamoxifen, can be delivered to the breast through the skin, and a phase IIb study comparing oral versus topical tamoxifen for DCIS.

The study authors have no conflicts of interest or disclosures to report.

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