50 Women’s Health FAMILY P RACTICE N EWS • February 15, 2005 Zoledronic Acid Sustains Bone in Breast Ca Patients

ARTICLES BY But prophylactic zoledronic acid appears to erase that who got zoledronic acid upfront and decreased in those BRUCE JANCIN downside. assigned to delayed bisphosphonate therapy. Biochemical Denver Bureau While it is widely appreciated that postmenopausal markers of bone turnover decreased from baseline to 6 breast cancer patients face increased risk of accelerated months in the upfront zoledronic acid group, while in- S AN A NTONIO — Zoledronic acid prevents the pro- bone loss, the osseus impact of cancer therapies in pre- creasing or remaining unchanged in the delayed treat- found loss in bone mineral density that often occurs with menopausal breast cancer patients ment arm. combined adjuvant endocrine therapy in premenopausal was much less clear before ABC- These early findings suggest ad- breast cancer patients, Michael Gnant, M.D., reported at SG-12. The primary end point in Patients on either ministration of zoledronic acid the annual breast cancer symposium sponsored by the the 1,315-patient Phase-III Austri- combination who from the onset of adjuvant aro- Cancer Therapy and Research Center. an study will be relapse-free sur- received matase inhibitor therapy may pre- Based on new data from the Austrian Breast and Col- vival, which awaits longer follow- zoledronic acid vent cancer therapy–induced bone orectal Cancer Study Group Trial 12 (ABCSG-12), all pre- up. In San Antonio, Dr. Gnant had no significant loss in postmenopausal women. menopausal breast cancer patients receiving combination reported on a secondary study end change in BMD. However, longer-term follow-up adjuvant therapy with a luteinizing hormone-releasing point—change in BMD—in a 401- is needed to fully define the effects hormone analog, such as goserelin plus either tamoxifen patient subset. DR. GNANT of zoledronic acid in this popula- or an aromatase inhibitor, should undergo annual bone The ABCSG-12 trial is a 4-part tion. The Novartis-sponsored Z- mineral density (BMD) testing. Those showing a treat- study that randomized patients to 3 years of adjuvant FAST trial is scheduled for 5 years of follow-up, said Dr. ment-related decline should be considered for intra- goserelin plus either tamoxifen or anastrozole, with or Brufsky of the University of Pittsburgh. venous zoledronic acid (Zometa) administered once without 3 years of zoledronic acid given at 4 mg IV every Zoledronic acid is more expensive than pamidronate every 6 months, said Dr. Gnant, professor of surgery at 6 months. After 3 years of goserelin and tamoxifen with- (Aredia), the other intravenous bisphosphonate, but its in- the University of Vienna. out zoledronic acid, BMD at the lumbar spine fell an av- fusion time is only 15 minutes, compared with 2 hours In a separate study presented at the conference, it was erage of 11.6%, compared with baseline. In patients re- or more for pamidronate, and there are some data to sug- reported that zoledronic acid also effectively prevents can- ceiving goserelin plus anastrozole but not zoledronic acid, gest zoledronic acid is more effective. cer therapy-induced bone loss in postmenopausal women it fell 17.4%. However, patients on either combination Until zoledronic acid receives an indication from the with early-stage breast cancer on adjuvant aromatase in- who received the potent intravenous bisphosphonate ex- Food and Drug Administration for use in the setting of hibitor therapy. perienced no significant change in BMD, the surgeon said. adjuvant breast cancer therapy, however, many oncolo- In clinical practice, the aromatase inhibitors increas- Separately, Adam Brufsky, M.D., presented preliminary gists will continue to follow the American Society for ingly are replacing tamoxifen, long the standard adjuvant 6-month results from Z-FAST, a multicenter U.S. trial in Clinical Oncology’s recent guidelines. Those call for in- hormonal therapy, because they provide a markedly which 415 postmenopausal women with early-stage hor- creased diligence in screening breast cancer patients for greater reduction in recurrence along with less risk of en- mone receptor–positive breast cancer receiving adjuvant bone loss, advising them on the importance of calcium dometrial cancer and thromboembolic events. letrozole (Femara) were randomized to zoledronic acid and vitamin D supplementation and bone-healthy lifestyle The price for these advantages has been the greater risk administered every 6 months either upfront or beginning measures, and the early use of the clearly less potent oral of osteoporosis and fractures associated with aromatase 1 year after the start of the aromatase inhibitor. bisphosphonates in women who show cancer treatment- inhibitor therapy. BMD at the lumbar spine and hip increased in patients related decline in BMD. Switch Out Tamoxifen to Improve Ca Outcomes More Educated Breast Ca Patients S AN A NTONIO — Switching post- als were postmenopausal, had hormone re- rector of the Cancer Research UK Labora- menopausal breast cancer patients to an aro- ceptor–positive disease, and underwent tories at Imperial College, London. Use More CAM matase inhibitor following 2-3 years of ad- breast-conserving therapy. One-fourth were Based upon the highly favorable IES data, juvant tamoxifen results in markedly better node positive. None received chemothera- Pfizer announced it has submitted a sup- S AN A NTONIO — The more disease-free survival than the traditional 5 py. Forty percent were under 60 years old. plemental New Drug Application seeking years of formal education a breast full years of tamoxifen, according to three Most had small, well-differentiated tumors. Food and Drug Administration approval cancer patient has, the more like- major randomized trials presented at a In a separate presentation, Charles for exemestane as adjuvant therapy in post- ly she is to use complementary breast cancer symposium sponsored by the Coombes, M.D., gave an update on the In- menopausal women with hormone recep- and alternative medicine in con- Cancer Therapy and Research Center. tergroup Exemestane Study (IES), in which tor–positive early-stage breast cancer. At junction with adjuvant chemother- Raimund Jakesz, M.D., recommended 4,740 postmenopausal breast cancer patients present, tamoxifen and anastrozole are the apy, Eleanor Glass reported at the that breast cancer pa- were randomized to 5 sole drugs with that indication. annual breast cancer symposium tients who fit the The likelihood of years of adjuvant ta- A midcourse switch from tamoxifen to an sponsored by the Cancer Therapy profile of partici- survival free of moxifen or switched aromatase inhibitor makes a lot of sense, and Research Center. pants in two Euro- distant recurrence to exemestane (Aro- Hope S. Rugo, M.D., said at a satellite sym- Her survey of 700 breast cancer pean clinical trials he was 39% greater masin) after 2-3 years. posium held in conjunction with the San An- patients who received chemothera- reported on at the with tamoxifen At a median 37 tonio conference. Tamoxifen is of proven py and/or adjuvant hormone ther- conference be rou- followed by months’ follow-up, lo- benefit in preventing recurrent breast cancer. apy showed that the majority— tinely switched to 3 anastrozole. cal or distant recur- It’s a good drug with favorable ancillary ef- 55%—used complementary and years of anastrozole rence had developed fects on bone mineral density and the car- alternative medicine (CAM) before, (Arimidex) after 2 DR. JAKESZ in 264 women treated diovascular risk profile. But resistance can oc- during, or afterward. A total of 27% years of tamoxifen. with tamoxifen and cur as early as 12-18 months after starting. of patients reported using CAM He reported on more than 3,100 breast 193 switched to the aromatase inhibitor. That Plus, the most serious side effects associ- during all three time periods. cancer patients in the AstraZeneca-spon- translated into a 27% increase in disease-free ated with tamoxifen—endometrial cancer CAM usage was strongly relat- sored Austrian Breast and Colorectal Cancer survival in patients who switched. Twelve cas- and thromboembolism—become more like- ed to education level. Overall, 30% Study Group Trial 8 and the German Adju- es of contralateral breast cancer occurred in ly with longer treatment. Stopping tamox- of patients without a high school vant Breast Cancer Group ARNO 95 study the tamoxifen/exemestane group vs. 26 in ifen early might prevent some of these ma- degree reported using CAM, as who were randomized to the standard 5 those on tamoxifen alone. jor adverse events while still providing did 50% with a high school de- years of adjuvant tamoxifen or to 2 years of A particularly intriguing finding is that protection against the increased fracture gree, more than two-thirds of tamoxifen followed by 3 years of anastrozole. there have been significantly fewer new pri- risk associated with 5 years of anastrozole in women with a college degree, and The 3-year rate of freedom from locore- mary cancers at sites other than the breast the Arimidex, Tamoxifen, Alone or in Com- 70% with graduate education, said gional recurrence, distant metastasis, and with exemestane: 46 vs. 59 in the tamoxifen- bination (ATAC) trial, said Dr. Rugo, direc- Ms. Glass of the University of contralateral breast cancer was 95.8% with ta- only arm. There have been 6 cases of lung tor of the breast oncology clinical trials pro- Cincinnati. moxifen/anastrozole vs. 92.7% with tamox- cancer with tamoxifen/exemestane vs. 13 gram at the University of California, San The most commonly used CAM ifen. The likelihood of survival free of distant with tamoxifen, and 2 cases of melanoma vs. Francisco, Comprehensive Cancer Center. therapies, in descending order of recurrence was 39% greater with tamoxifen 5 cases with tamoxifen only. However, 20 To date the switch trials have shown a frequency, were vitamin E, vitamin followed by anastrozole, said Dr. Jakesz, pro- acute MIs have occurred in patients switched higher incidence of osteoporosis but not a C, vitamin B6, green tea, selenium, fessor of surgery at the University of Vienna. to the aromatase inhibitor vs. 8 MIs in the significant rise in fractures, compared with echinacea, garlic extract, soy sup- All participants in the two randomized tri- tamoxifen-only group, said Dr. Coombes, di- 5 years of tamoxifen alone, she noted. plements, and ginkgo biloba.

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