Surgery News - February 2008 - (Page 16)

BREAST, SKIN & SOF T TISSUE SURGERY NEWS • F E B R U A RY 2 0 0 8 Anastrozole Curbs Breast Cancer Recurrence for Years analysis by the Early Breast Cancer Trialists’ Collaborative Group had already established that tamoxifen, too, has a carryover effect. Indeed, tamoxifen was roughly 33% S A N A N T O N I O — The efficacy of the aromatase in- more effective than placebo at preventing recurrences durhibitor anastrozole for prevention of breast cancer re- ing the first 5 years following completion of therapy. A key finding in the 100-month ATAC follow-up is that currence persists for years after treatment completion— but the side effects do not, according to the 100-month the earlier nonsignificant trend for fewer contralateral canfollow-up analysis of the landmark Arimidex, Tamoxifen, cers with anastrozole at 5 years has attained significance. By 9 years the contralateral breast cancer rate Alone or in Combination (ATAC) trial. was 2.5% with anastrozole, compared with “This is the first demonstration of a carry4.2% with tamoxifen. This finding, coupled over effect for an aromatase inhibitor,” Dr. with the demonstrated carryover effect, has John F. Forbes said in presenting the median profound implications. 100-month ATAC data at the annual San An“It’s plausible that as primary preventive tonio Breast Cancer Symposium. agents, the aromatase inhibitors—in this case, ATAC is a double-blind, 21-nation clinical anastrozole—could have a substantial effect in trial in which 6,241 postmenopausal women preventing hormone-sensitive breast cancer in with invasive breast cancer were randomized women at high risk,” Dr. Forbes said. to 5 years of anastrozole or tamoxifen, a drug Ten percent of the anastrozole group exwith a well-established track record in reduc- Anastrozole ‘could ing recurrence risk in patients with hormone have a substantial perienced a fracture during the 5 years of receptor–positive disease. effect in preventing treatment, a rate roughly 50% greater than At the 5-year mark in the more than 5,200 hormone-sensitive with tamoxifen. Once patients finished treatment, however, the increased fracture risk asATAC participants with hormone receptor–posbreast cancer in sociated with aromatase inhibitor therapy itive breast cancer, the recurrence rate was women at risk.’ completely disappeared; there were 146 frac9.7% in the anastrozole group and 12.5% in the DR. FORBES ture episodes off-treatment in the anastrotamoxifen arm, for a highly significant absolute 2.8% difference favoring anastrozole. This difference has zole group and 143 in the tamoxifen group. Patients have expanded to 4.8% at 9 years in the new update. During remained blinded as to their former adjuvant treatment 46,292 woman-years of follow-up, breast cancer recurred since going off-treatment. No new morbidity or mortality issues have arisen durin 17% of patients in the anastrozole arm, compared to 21.8% with tamoxifen, reported Dr. Forbes, professor of ing post-treatment follow-up. The total mortality rate at 9 years was 20% in both groups. medicine at the University of Newcastle (Australia). Dr. Forbes highlighted the surprisingly low endometrial The recurrence risk during the 5 years on treatment was 23% lower with anastrozole than tamoxifen. During cancer rate in the anastrozole group post treatment as an the next 4 years the recurrence risk was 25% less in the intriguing finding worthy of further investigation. Offanastrozole group than with tamoxifen. That’s a partic- treatment there has been just 1 case of endometrial canularly noteworthy finding because a comprehensive meta- cer in the anastrozole arm, compared with 12 in the taBY BRUCE JANCIN Else vier Global Medical Ne ws moxifen group. There were 4 cases on-treatment in the anastrozole group and 12 with tamoxifen, which has endometrial cancer as a major side effect. “This may be the first evidence that an aromatase inhibitor—in this case, anastrozole—may be a potential primary preventive agent for endometrial cancer,” he said. Audience member Dr. Eric Winer indicated he was underwhelmed by the latest ATAC data. “It seems to me that the headline is that there’s no difference in survival through 100 months of follow-up. I guess I’m struck that we need to pursue other avenues if indeed we’re going to reduce breast cancer mortality in this subgroup of women who have postmenopausal hormone receptor–positive breast cancer,” said Dr. Winer, director of the Breast Oncology Center at Harvard University’s Dana-Farber Cancer Center, Boston. Dr. Forbes replied, “Those of us who work in the clinics well know that the single major concern of women who’ve had breast cancer is fear of its return. So we shouldn’t underestimate the importance of this clearly established reduction in recurrence.” He stressed that hormone receptor–positive breast cancer in postmenopausal women is a very different disease in terms of biology and outcome than receptor-negative breast cancer in younger women, which tends to be more aggressive. He noted that at 100 months of follow-up the mean age of the ATAC participants was 72 years—an age when competing causes of death increasingly overshadow breast malignancy. “I think we have to accept that [postmenopausal hormone receptor–positive breast cancer] is a chronic problem. I think our strategies should be directed more at stopping it from coming back and let the survival look after itself because, quite simply, if a woman doesn’t have breast cancer she can’t die of it,” he added. Dr. Forbes is on the speakers bureaus of Novartis Oncology and AstraZeneca, which funds ATAC. ■ Accelerated Whole Breast Radiotherapy May Be Advantageous BY BRUCE JANCIN Else vier Global Medical Ne ws S A N A N T O N I O — Accelerated hypofractionated whole breast irradiation after breast-conserving cancer surgery produces late outcomes equal to standard radiotherapy, but with a substantial reduction in overall treatment time, according to the findings of a landmark Canadian clinical trial. “Accelerated hypofractionated whole breast irradiation offers an important advantage to women who wish to be treated in a shorter period of time. Results of our trial and other trials should encourage broader use of this proven modality,” Dr. Timothy Whelan said at the San Antonio Breast Cancer Symposium. Results of the 1,234-patient study conducted by the Ontario Clinical Oncology Group come at a time of growing concern among some experts regarding falling rates of radiation therapy following breastconserving surgery (BCS) for invasive breast cancer, despite its proven benefit in reducing local recurrence rates. Up to 30% of women skip radiotherapy following BCS. The most frequently cited reason is its inconvenience, which suggests that for many of these women, accelerated hypofractionated whole breast irradiation (AHWBI) could be a particularly attractive option that helps get adjuvant radiotherapy rates back on track, according to Dr. Whelan, professor of medicine at McMaster University, one-third of deaths in both groups were non–cancer related. Hamilton, Ont. At baseline, 83% of women had good or AHWBI is used widely in Canada, the United Kingdom, and much of Europe. It excellent cosmetic outcomes on a stanis used infrequently in the United States, dardized rating scale. This figure declined where there has been concern that the du- over time to 70% at 10 years but with no difference between the two ration of follow-up in the groups at any time point. Canadian and British randomRadiation-induced skin and ized trials showing equivalent soft tissue damage increased outcomes for AHWBI and over time such that the comstandard whole breast irradiabined rate of moderate to tion (SWBI) has been too brief marked morbidity at 10 years’ to rule out the possibility of a follow-up was 12% in both late increase in AHWBI-associgroups. However, not a single ated cancers and/or cosmetic woman developed severe breast deformities. skin/soft tissue morbidity with Those concerns have now Reassuringly, at been addressed by the updated 10 years, the local necrosis or ulceration. Although numerous innovaresults of the Ontario trial, fearecurrence rate tions designed to reduce the turing a median 12-year followwas 6.7% with morbidity and/or inconveup, Dr. Whelan continued. The SWBI and 6.2% nience of radiotherapy have study involved 1,234 women with AHWBI. been developed—including parwho underwent BCS for earlyDR. WHELAN tial-breast irradiation, brachystage invasive carcinoma, then were randomized to an SWBI regimen therapy, and intraoperative radiotherapy— consisting of 50 Gy delivered in 25 frac- to date only whole breast irradiation is tions over a total of 35 days or to backed by firm proof of efficacy as an inAHWBI with 42.5 Gy in 16 fractions over tegral part of breast-conserving therapy, Dr. Whelan stressed. 22 days. Dr. Laura J. Esserman, an ACS Fellow Reassuringly, at 10 years, the local recurrence rate was 6.7% with SWBI and who is also professor of surgery and radi6.2% with AHWBI. Ten-year overall sur- ology at the University of California, San vival was 84% in both treatment groups. Francisco, and director of the Carol Franc At a median 12 years of follow-up, total Buck Breast Care Center at the university, mortality was 20.6% with the SWBI regi- predicted the Canadian study will be pracmen and 19.6% with AHWBI. Roughly tice changing in the United States. But Dr. Lori Pierce said there should be some caution in extrapolating its results to everyone with stage I or II breast cancer treated with breast conservation. “The vast majority of our stage I/II patients [in the U.S.] receive chemotherapy [with or without hormonal therapy], whereas Canadians are more likely to give hormonal therapy only. There is concern that this study underestimates the potential toxicity of combining large fractions of RT and cytotoxic therapy,” said Dr. Pierce, associate provost for academic and faculty affairs professor at the University of Mich

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Surgery News - February 2008

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