1. Susman, Ed

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SAN ANTONIO-Breast cancer patients taking aromatase inhibitors to prevent disease recurrence are apparently at high risk of experiencing bone loss, an adverse effect of the new agents, researchers reported here at the 38th San Antonio Breast Cancer Symposium (Abstract P5-12-03).

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Remarkably, 16 percent of women developed bone loss while they were being treated with aromatase inhibitors, said Melissa Pirolli, MS, a senior principal in Oncology at IMS Health, a data service consulting company based in Plymouth Meeting, Pennsylvania. Another 37 percent of women showed evidence of bone loss before they began therapy with aromatase inhibitors, shown to be superior to tamoxifen in preventing breast cancer recurrence, Pirolli said at her poster presentation.


Study Details

For the study, sponsored by Amgen, Pirolli and her colleagues accessed the Oncology Services Comprehensive Electronic Records (OSCER) database of more than half a million individuals with a cancer diagnosis from 52 oncology practices. Specifically, the OSCER database was used to identify women who had invasive breast cancer.


OSCER allows projection nationally through methods of direct estimations utilizing claims data. When projected to the U.S. population, it is estimated that 538,630 women with non-metastatic breast cancer were treated with an aromatase inhibitor in 2014, representing a median of six prescriptions in 2014. About 87 percent of these women filled two or more aromatase inhibitor prescriptions.


Of these prescriptions, 94 percent were anastrazole or letrozole. About 55 percent of the women were 65 years of age or older, and 11 percent took tamoxifen prior to their first aromatase inhibitor. Among women taking aromatase inhibitors in 2014, about 39 percent of them initiated the therapy in 2014, 24 percent initiated therapy in 2013, and 37 percent have been on aromatase inhibitors since 2012 or earlier, Pirolli told OT.


"Adjuvant endocrine therapy compromises bone health in patients with breast cancer, leading to osteopenia, osteoporosis, and fractures," Pirolli said. "But for postmenopausal women with estrogen receptor-positive breast cancer, aromatase inhibitors have emerged as the standard of care because of superior efficacy over selective estrogen receptor modulators such as tamoxifen."


And she said rates of utilization and duration of aromatase inhibitor therapy are expected to continue to increase. "This study provides current estimates of the prevalence of non-metastatic breast cancer treated with aromatase inhibitors in the United States using real-world data. Thirty-seven percent of women on endocrine therapy have been on it since 2012 or earlier, and continued use of aromatase inhibitors will likely lead to increased patients with bone loss," Pirolli said.


"Women on aromatase inhibitor therapy face an increased risk of fractures, highlighting the need for intervention with antiresorptive treatments. Bisphosphonates have been studied and denosumab has a labeled indication in this setting. These agents may help build bone mass and counteract detrimental effects on the bone," she suggested.


In Agreement

Eleonora Teplinsky, MD, a medical oncologist at Northwell Health Cancer Institute, Lake Success, New York, concurred with the findings in the study. "Bone loss is a significant adverse effect seen with aromatase inhibitor therapy," she told OT. "Pirolli et al. evaluated over 530,000 women treated with aromatase inhibitors and showed that 285,543 patients receiving an aromatase inhibitor had evidence of bone loss, with 16 percent of them developing this bone loss only after exposure to an aromatase inhibitor. Awareness of this potential toxicity is critical, as certain patients will need treatment with antiresorptive therapies."


Confirmation, Clarification

In performing the study, Pirolli scrutinized the electronic records, seeking codes of confirmed diagnosis of invasive breast cancer. The researchers excluded women with codes that indicated they had metastatic disease, and confirmed they were being treated with aromatase inhibitors in 2014. Bone loss was defined by diagnosis of osteoporosis, osteopenia or receipt of bone therapy in 2014. Bone therapies used as proxy for bone loss were intravenous ibandronate and zoledronic acid or oral bisphosphonates such as risedronate, ibandronate, etidronate, or alendronate, or subcutaneous anti-RANK ligand antibody denosumab.


Pirolli estimated that the 2014 prevalence of non-metastatic breast cancer patients on aromatase inhibitor therapy in the United States was 538,630. There were an estimated 468,608 women who filled at least two prescriptions of aromatase inhibitors; evidence of bone loss in these women before starting aromatase inhibitor therapy was 199,846. Bone loss after starting aromatase inhibitor therapy was observed in 85,697 women, she said.

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Most of the women with bone loss were ages 55 and older. About 25 percent of the women in the decade of 55-64 years had bone loss. More than half the women aged 65 years or older were found to have bone loss. "It is not necessarily a surprise that older women were the ones who experienced much of the bone loss," Pirolli said.


Noting that many women complain about musculoskeletal aches and pains while being on aromatase inhibitor therapy, Pirolli said whether those aches and pains are related to bone loss is difficult to answer.


"I can't say the answer to that question with the data we have," she said. "We have studies not yet published that are looking at different pain scale questionnaires filled out by patients when they came into the office on how they were feeling that day. So these studies are in the works. The study we are presenting here was built using information from electronic health records, so it doesn't have patient reported outcomes."