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16 WOMEN’S HEALTH JANUARY 15, 2009 • INTERNAL MEDICINE NEWS Density Predicts Drug’s Preventive Benefit

BY BRUCE JANCIN moxifen because of concerns about toxi- Among the roughly 40% of - 2.7-fold increased risk of , Denver Bureau city. The new IBIS-I findings have the po- treated subjects who showed at least a while a density in the 76%-100% range tential to increase adoption of tamoxifen 10% reduction in breast density at their conferred a 3.9-fold increased risk. S AN A NTONIO — A reduction in therapy in eligible women because after 12- to 18-month mammograms, there Dr. Cuzick stressed that the new find- mammographic breast density after 12- just 12-18 months they’ll have a good in- was a 63% reduction in breast cancer risk ings apply specifically to tamoxifen for 18 months of tamoxifen use—prescribed dication of whether it’s working for them. compared with placebo after adjustment prevention. Whether the same holds for primary prevention of breast can- IBIS-I randomized 7,154 women at for age, body mass index, and baseline true for tamoxifen in the adjuvant setting cer—is an excellent early predictor of high risk for breast cancer to 5 years of breast density. In contrast, tamoxifen- in women being treated for breast can- subsequent treatment efficacy, according tamoxifen or placebo. At the latest fol- treated women who did not have at least cer remains to be seen. to a new report from the landmark In- low-up, the tamoxifen group had a sig- a 10% reduction in breast density went Dr. Cuzick is now looking at the on- ternational Breast Intervention Study I. on to have essentially the same breast going IBIS-II trial database to learn Women who showed at least a 10% de- ‘This is the first cancer incidence as did those on placebo. whether early change in breast density is crease in breast density by visual assess- time in cancer In an analysis restricted to participants also a predictor of efficacy for the aro- ment on routine mammography 12-18 we’ve found a with baseline atypical hyperplasia or lob- matase inhibitor (Arimidex) months into their 5-year course of ta- biomarker that ular carcinoma in situ, a 10% or greater when used for primary prevention in moxifen experienced a 63% reduction in predicts response decrease in breast density in response to high-risk postmenopausal women. It will breast cancers compared with placebo to preventive tamoxifen was associated with a 71% re- also be important to scrutinize mam- through 8 years of follow-up in IBIS-I, treatment.’ duction in breast cancer risk compared mograms collected in the clinical trials Jack Cuzick, Ph.D., reported at the San with placebo, Dr. Cuzick continued. that led to approval of (Evista) Antonio Breast Cancer Symposium. DR. CUZICK “Mammographic density is a very sim- for breast cancer prevention in high-risk “This is the first time in cancer we’ve ple thing to measure that really isn’t women to determine whether change in found a biomarker that predicts response nificant 27% decrease in breast cancer very much used at the moment,” he breast density is predictive of efficacy for to preventive treatment. ... The point is, risk (J. Natl. Cancer Inst. 2007;99:272-82). noted in an interview. Visual estimates of that drug as well. if your preventive intervention doesn’t The new mammographic density breast density to the nearest 5% as em- “If this turns out to be a general phe- work, there’s no point in pressing on for analysis included 126 IBIS-I participants ployed in IBIS-I show “very good” re- nomenon that applies to any kind of pre- 5 years,” explained Dr. Cuzick, chair- who developed breast cancer after their producibility, Dr. Cuzick added. ventive activity, it might mean we can be- man of the IBIS-I steering committee 12- to 18-month mammogram and 942 Multiple studies have established that gin to evaluate breast cancer preventive and head of the Cancer Research UK controls who remained free of breast baseline breast density has the highest at- strategies in trials of 1-2 years rather than Centre for Epidemiology, Mathematics, cancer during the first 5 years of the tributable risk of all known breast cancer 10 years to find out if something works,” and Statistics, London. study. At baseline, 47% of the women risk factors. In an earlier IBIS-I analysis, Dr. Cuzick said. Many healthy women at high risk for had at least 50% of their covered a baseline density of 51%-75% was an in- Dr. Cuzick said he has no financial con- breast cancer are reluctant to take ta- by densities. dependent risk factor associated with a flicts of interest regarding the study. ■ Complication Rate Low Lasofoxifene Shown to Sharply Brachytherapy from page 1

15, or 20 years ago are growing guidance using a template with Reduce Incidence of Breast Cancer into the age where they are de- predrilled holes to map catheter veloping breast cancer,” said positioning. The catheters rest BY BRUCE JANCIN tebral fractures, which were de- among women with above-av- Dr. Kuske, noting that one- on the surface of the augmen- Denver Bureau creased by a highly significant erage levels of . Other third of his patients have had tation, Dr. Kuske noted, but no 24% in women randomized to benefits included a reduction of breast augmentation. punctures occurred in any of S AN A NTONIO — The in- lasofoxifene at 0.5 mg/day. 42% in vertebral fractures, a Previous trials have shown the patients. The target volume vestigational selective - The PEARL participants decrease of 32% in major coro- excellent overall outcomes and was the lumpectomy cavity lasofox- (aged 59-80 years) were enrolled nary heart disease events, and in-breast control rates with plus 2 cm. Treatment was de- ifene is shaping up as a PEARL in 32 countries. All had osteo- a 36% reduction in strokes. multicatheter brachytherapy livered with 34 Gy in 10 frac- of a drug for the prevention of porosis at entry. They were ran- The chief risk associated with following lumpectomy in pa- tions twice daily over 5 days breast cancer. domized to placebo or lasofox- the SERM was a twofold in- tients with selected early-stage with high-dose–rate iridium Lasofoxifene (Fablyn) slashed ifene at 0.25 or 0.5 mg/day. crease in venous thromboem- cancers (Int. J. Radiat. Oncol. 192. The end points evaluated the incidence of estrogen re- During 5 years of follow-up, bolic events (from 0.4% over 5 Biol. Phys. 2008;72:467-73). The were tumor control, complica- ceptor–positive breast cancer 21 women in the placebo arm years in the placebo arm to results presented at the RSNA tions, and cosmesis. by 81%, compared with place- developed – 0.8% with 0.5 mg lasofoxifene). meeting provide the first evi- No breast or nodal recur- bo, over a 5-year period in the positive breast cancer, as did 11 In September 2008, the Food dence of brachytherapy’s po- rence or capsular contracture 8,556-woman, phase III PEARL in the lower-dose and 4 in the and Drug Administration’s Re- tential as an early-stage treat- was noted in any of the pa- (Postmenopausal Evaluation higher-dose lasofoxifene arms. productive Health Advisory ment alternative for women tients after a median follow-up and Risk Reduction With La- The incidence was 0.3 cases per Committee recommended ap- with saline or silicone breast time of 26 months (range of 3- sofoxifene) trial, Andrea Z. 1,000 patient-years in women proval of Inc.’s applica- implants. So far, “early tumor 60 months). Cosmesis ratings LaCroix, Ph.D., reported at the on lasofoxifene at 0.5 mg/day, tion for an indication for laso- control is 100% [in this group of were either excellent (91%) or San Antonio Breast Cancer 0.9 cases per 1,000 patient-years foxifene at the 5-mg dose for patients], but obviously more good (9%) for all patients. Symposium. with lasofoxifene at 0.25 treatment of . follow-up is necessary,” Dr. Clinical infections, a concern That’s a considerably more mg/day, and 1.9 cases per 1,000 One oncologist in the San An- Kuske said. with multicatheter placement, dramatic preventive effect than patient-years with placebo. tonio audience shrugged off Between June 2003 and June occurred in four patients, and all the roughly 50% reductions Women on lasofoxifene at Pfizer’s failure to seek an addi- 2008, 70 patients (median age were successfully treated with seen in earlier placebo-con- 0.5 mg/day had a 35% reduc- tional indication for breast can- 50 years) were treated with antibiotics. More than half of trolled trials of tamoxifen and tion in breast biopsies, com- cer prevention, noting that multicatheter brachytherapy patients (40) received brachy- raloxifene, the two approved pared with the 2.8% incidence once lasofoxifene is approved following lumpectomy in se- therapy without antibiotics; 26 agents for primary prevention in the placebo arm. As expect- for osteoporosis, physicians lect early-stage cancers. Eligi- patients received antibiotics pro- of breast cancer, added Dr. ed, the SERM had no effect on will readily be able to prescribe bility criteria were stage I or II phylactically. Other complica- LaCroix, a professor of epi- the rate of estrogen recep- the drug in postmenopausal breast carcinoma confirmed to tions included one wound de- demiology at the University of tor–negative breast cancers. women for breast cancer pre- be less than 3 cm, and 0-3 pos- hiscence, two minor cases of Washington, Seattle. The risk of ductal carcinoma in vention as well. itive axillary nodes without ex- telangiectasia, one pneumotho- Reduction of estrogen re- situ was similarly unaffected. Dr. LaCroix disclosed that tracapsular extension. rax, and one persistent seroma. ceptor–positive breast cancer Dr. LaCroix noted that she is on the advisory boards A mean of 17 plastic cath- Dr. Kuske is a consultant for was a coprimary end point in lasofoxifene had its greatest for Pfizer, Sanofi-Aventis, and eters were placed with CT Nucletron. ■ PEARL, together with nonver- breast cancer reduction benefit Procter & Gamble Co. ■

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