SABCS: Endocrine Breast Cancer Therapy Raises Questions

SAN ANTONIO, Dec. 19 -- The advent of endocrine therapy for breast cancer has raised a host of unanswered questions about who should get the new drugs, when, and what should be done about treatment side effects, researchers said here.

In pre-menopausal women, tamoxifen remains a standard therapy for estrogen receptor-positive cancer, said Nancy Davidson, M.D., of the Sidney Kimmel Comprehensive Cancer Center at Johns Hopkins in Baltimore.

For these women, chemotherapy is usually the first line of treatment, followed by tamoxifen, but the "thorniest question" is whether chemotherapy should be used at all, Dr. Davidson told a satellite symposium at the San Antonio Breast Cancer Symposium. The session was organized by Vanderbilt University School of Medicine and Drexel University College of Medicine, with financial support from Cytogen Corp. of Princeton, N.J.

If physicians were to start fresh with all the modern options, she said, "We might have started with the endocrine therapy and then looked at the value of chemotherapy on top."

She added that the whole question of the optimal sequence of treatment for pre-menopausal women remains unclear but is under active investigation in several major randomized trials.

Options being studied include ovarian suppression plus an aromatase inhibitor, tamoxifen plus ovarian suppression, aromatase inhibitors plus ovarian suppression, and ovarian suppression with tamoxifen, aromatase inhibitors and chemotherapy.

Among the questions, she said, is the duration of ovarian suppression when - and if - it is used. "We're really in the dark about how long to use ovarian suppression techniques," she said.

The situation is somewhat clearer in post-menopausal women, said Paula Ryan, M.D., Ph.D., of Massachusetts General Hospital in Boston, but key questions include the optimal duration and timing of endocrine therapy.

Breast cancer is primarily a disease of older women, she said, with 74% of cases in post-menopausal women. The aromatase inhibitors are not usually recommended in women younger than 40, but are more and more commonly used in post-menopausal women.

The advent of the aromatase inhibitors has raised the questions of whether tamoxifen should be used at all, first, or for how long, she said, and a range of clinical studies are now trying to tease out some answers.

Studies have hinted that the aromatase inhibitors "have won some battles over tamoxifen," Dr. Ryan said, but the jury is still out, mainly because experience with these drugs is still essentially short-term.

In this population, she said, therapy is expected to continue for 15 or more years, which makes the issue of long-term toxicity "critically important."

The aromatase inhibitors, by and large, have only been used for a few years so that "we are still, in my opinion, in the short-term side effect arena," Dr. Ryan said.

The side effects of therapy - regardless of which medications are used -- are a key issue for physicians, said Patricia LoRusso, D.O., of Wayne State University School of Medicine.

One key issue - and one often ignored - is dryness, Dr. LoRusso said. Many therapies cause dry mouth, dry skin and vaginal dryness. For many women, the vaginal dryness - associated with aromatase inhibitors and tamoxifen - can be a serious obstacle to therapy.

"It's the main problem we hear over and over again," she said.

Especially in younger women, she said, such changes can lead to sexual dysfunction, which can in turn lead to difficulties in relationships and subsequent depression. Physicians need to ask about such issues and even such a simple remedy as vaginal lubricants can help patients, she said.

Bone loss is also a concern, she said, which can be addressed by carefully monitoring bone mineral density and by treating with bisphosphonates when indicated.

Depression and other psychiatric issues are common among breast cancer survivors, Dr. LoRusso said, with the prevalence of a specific diagnosis ranging from 1.5% to 57%, depending on which study is cited.

Education is a key element of the treatment plan, she said. Physicians must ensure that patients are aware of the possibility of some of these symptoms, so they are not taken by surprise.