SABCS: More Evidence that Bisphosphonates Prevent Breast Cancer

SAN ANTONIO (MedPage Today) -- Women taking oral osteoporosis drugs had a 30% lower risk of breast cancer than women who didn't take them, according to data from two different retrospective studies.

Data from the U.S. Women's Health Initiative (WHI) showed an overall risk reduction, a significant reduction in the risk of receptor-positive breast cancer, and a trend toward a lower risk of receptor-negative breast cancer in women taking a bisphosphonate, Los Angeles cancer researcher Rowan Chlebowski, MD, reported at the San Antonio Breast Cancer Symposium.

Confounding the results, bisphosphonate treatment was associated with an increased risk of ductal carcinoma in situ, a finding for which Chlebowski had no explanation.

An Israeli study showed that the drugs' beneficial effect on breast cancer risk began after a year of treatment and then remained stable with continued use of the drugs. Moreover, women who developed breast cancer while taking a bisphosphonate had tumors with prognostically favorable characteristics.

Despite the positive findings, Chlebowski, of Harbor-UCLA Medical Center, and Gad Rennert, MD, PhD, of Carmel Medical Center in Haifa, urged caution in judging the implications for breast cancer prevention.

"This is an association study; it's not a study of proof," said Rennert. "We are raising a hypothesis."

Prospective, randomized clinical studies are needed to determine whether bisphosphonate drugs have a role in breast cancer prevention, he added.

A study reported at the 2008 San Antonio meeting provided evidence that an intravenous bisphosphonate might have a direct anticancer effect on breast tumors. The studies reported by Chlebowski and Rennert extended the association to oral bisphosphonates.

Chlebowski's analysis focused on 10,000 WHI participants whose medical records included results of bone-mineral density studies. Of those, 2,216 were taking bisphosphonates at enrollment.

An age-adjusted analysis showed that women taking an oral bisphosphonate had a breast cancer rate of 3.29 per 1,000 person-years. That compared with 4.38 per 1,000 person-years among women who were not taking a bisphosphonate. The difference represented a statistically significant 31% reduction in the incidence of invasive breast cancer (HR 0.69, P<0.01).

When the cancers were categorized by receptor status, women taking bisphosphonates had a 30% lower incidence of receptor-positive breast cancers (HR 0.70, P=0.01).

The risk of receptor-negative breast cancer was 32% lower in the bisphosphonate group, but the difference did not achieve statistical significance, primarily because of the low rate of ER-negative cancer (0.61 per 1,000 person-years in women not taking bisphosphonates versus 0.41 in the bisphosphonate group).

Analysis of in situ cancer incidence produced the surprising findings of an increased risk in bisphosphonate users: 1.53 versus 0.92 per 1,000 person-years. The difference translated into a 41% greater incidence compared with women who were not using bisphosphonates (HR 1.59, P=0.002).

The findings could mean that bisphosphonates prevent invasive but not in situ breast cancer, prevent the progression of in situ cancer to invasive cancer, or something entirely different, said Chlebowski. Other studies are needed to clarify the findings.

Rennert presented data from an analysis of 4,575 postmenopausal patients participating in a population-based study of breast cancer. Investigators compared breast cancer rates in women who used bisphosphonates for five years or more versus women who did not use bisphosphonates.

Investigators analyzed the data in two ways: patients' self-reported use of bisphosphonates and use documented by pharmacy records. Two analyses yielded consistent outcomes.

By self-report, bisphosphonate use was associated with a 34% reduction in breast cancer incidence. Pharmacy records suggested a 28% reduction. Both differences were statistically significant.

The cancer-reducing effect of bisphosphonate treatment appeared after a year of use, said Rennert. The magnitude of the benefit increased negligibly with use beyond a year.

Investigators also found that breast cancers that developed in bisphosphonate users were more likely to have favorable characteristics: in situ versus invasive cancer, moderately or well differentiated, strong ER positivity, and HER2 negativity.

Chlebowski disclosed relatinships with AstraZeneca, Novartis, Pfizer, Amgen, and Lilly. Renner had no disclosures.

Primary source: San Antonio Breast Cancer Symposium Source reference: Chlebowski R, et al "Oral bisphosphonates and breast cancer: Prospective results from the Women's Health Initiative (WHI)" SABCS 2009; Abstract 21.Additional source: San Antonio Breast Cancer SymposiumSource reference: Rennert G, et al "Use of bisphosphonates and risk of postmenopausal breast cancer" SABCS 2009; Abstract 27.