Breast Cancer Symposium Features Surgical Data, Updated Results from BOLERO-2, and Other Important News


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The annual Breast Cancer Symposium, held September 13 to 15 in San Francisco, is jointly sponsored by ASCO, the American Society for Radiation Oncology, the American Society of Breast Disease, the American Society of Breast Surgeons, the National Consortium of Breast Cancers, and the Society of Surgical Oncology. The conference  allows for close interaction with thought leaders in multiple disciplines as well as an upfront view of advances in the field, a few of which are summarized in this meeting roundup.

Time to Specimen Fixation May Impact Tumor Estrogen Receptor Status

A retrospective review of surgeries performed between 2008 and 2011 at the Mayo Clinic, Rochester, showed that the time to tissue fixation varies significantly among surgeons and can affect estrogen receptor status of the tumor.9 Longer time to fixation (> 60 vs ≤ 60 minutes) was associated with greater odds of estrogen receptor negativity (64.6% vs 35.4%, P = .03).

In a multivariate analysis, time to fixation was an independent predictor of estrogen receptor status. If prolonged, time to fixation leads to false-negative estrogen receptor staining, and patients may not receive appropriate treatment. In-service training was effective at shortening the time to fixation.

BOLERO-2: 18-month Data

Updated results from the pivotal phase III BOLERO-2 trial continue to show that everolimus (Afinitor) added to exemestane in metastatic breast cancer significantly delays disease progression.1 Median progression-free survival by local assessment was 7.8 months with everolimus/exemestane vs 3.2 months with exemestane alone, for a 55% reduction in risk. By central review, median progression-free survival was 11.0 vs 4.1 months, respectively, for a 62% reduction in risk. The differences in each analysis were highly significant (P < .0001).

While no significant differences in overall survival have emerged, with 200 deaths overall there were 6.8% more deaths with single-agent therapy, reported Hope Rugo, MD, of the University of California, San Francisco.

An exploratory analysis of the trial suggested that adding everolimus has beneficial effects on bone turnover and breast cancer progression in the bone.2 Bone marker levels at 6 and 12 weeks increased over baseline levels with placebo, but decreased with everolimus, for an absolute difference of 66%. At day 60, the cumulative incidence rate of progressive disease in the bone was also lower with everolimus (3.03% vs 6.16%), and this trend was sustained beyond 6 months. The investigators suggested that everolimus is overcoming the negative effects that exemestane is known to have on bone.

“In the overall population, we saw less progression in the bone in patients getting everolimus, and in the subgroup with bone metastases at baseline—which is about three-quarters of patients—we saw this as well,” Dr. Rugo said. “This is a very interesting difference that suggests there is a site-specific effect with everolimus, and we have not seen this much with other targeted agents.”

Final Analysis of RIBBON-2

The final overall survival and safety analysis of the RIBBON-2 trial revealed no improvement in overall survival (a secondary endpoint) with the addition of bevacizumab (Avastin) to second-line chemotherapy in patients with HER2-negative, bevacizumab-naive metastatic breast cancer.3 Of the 684 patients, 82% in each arm have died. Median overall survival was 17.8 months with chemotherapy alone and 18.6 months with chemotherapy plus bevacizumab, and 1-year survival rates were 69% and 71%, respectively, reported Adam M. Brufsky, MD, of the University of Pittsburgh Cancer Institute.

An exploratory analysis of the triple-negative subset gave a hint of an overall survival benefit. Median survival was 17.8 months with bevacizumab vs 13.5 months with placebo, but the 15% risk reduction was not statistically significant. Updated safety results were similar to those previously reported.

“As you can tell, at this point there is no statistical basis for a survival benefit with bevacizumab in RIBBON-2. We should find the phase III TANIA trial interesting. The study is evaluating second-line bevacizumab in patients pretreated with bevacizumab, with bevacizumab extended beyond progression, which may be a rational design, according to preclinical data. As of yet, however, there is no basis for using bevacizumab beyond progression,” he said.

Some Staging Evaluations Mostly Useless

A systematic literature review found that staging evaluations with bone scans, liver ultrasound, and chest x-ray have a very low yield of metastatic disease.4 This raises questions as to the utility of routinely performing these studies, especially in asymptomatic patients with small tumors, the researchers suggested.

The detection rates with these modalities in patients with stage I/II tumors ranged from less than 0.5% to 3.0%. The yield was much greater in patients with stage III disease, for whom the detection rate was 12.5% with bone scans, 4.2% with liver ultrasound, and 4.6% with chest radiographs, reported Allison M. Staley, a medical student who presented the findings.

Thomas A. Buchholz, MD, of The University of Texas MD Anderson Cancer Center, Houston, commented as poster discussant, “This is a nice review supporting [National Comprehensive Cancer Network] guidelines, and it further demonstrates that most breast cancer patients do not need staging imaging for metastasis.”

Fewer Young Women Being Screened with Mammography

The U.S. Preventive Services Task Force recommendation that women aged 40 to 49 not undergo mammographic screening has had a strong impact on screening rates in this age group, but not in older women, according to a time-series analysis of administrative claims data from over 100 health plans.5 The analysis evaluated screening rates between January 2006 and January 2011 among 11.4 million women.

The baseline mammography rate was 39.3 per 1,000 in the 40- to 49-year-old age group, and 47.0 per 1,000 among women aged 50 to 64. The Task Force update was associated with a decrease in screening in the younger, but not the older, population. Among younger women, mammography screening rates fell by 7.59% at 2 months postupdate, by 5.33% at 1 year postupdate, and by 5.02% at 2 years postupdate. The reduction in screening among younger women translates into more than 90,000 fewer mammograms over the 2 years.

Other investigators asked whether young women at higher risk might be identified and thus recommended for screening.6 They applied the Gail model (see sidebar) to 223,349 women from the Screening Mammography Program of British Columbia, calculating the Gail score on these individuals and comparing it to the actual incidence of breast cancer. The Gail model was not effective in personalizing screening recommendations as it significantly underpredicted cancer detection. While it provided a sufficient fit for women with a Gail risk range between 1.51% and 4%, it did not predict cancer risk accurately for low-risk and high-risk women.

Data Support Accelerated Partial-breast Irradiation

In a matched-pair analysis, accelerated partial-breast irradiation (APBI) using a 2-day regimen yielded outcomes equivalent to the 5-day schema in a study of 114 patients.7 After a mean follow-up of almost 5 years, no differences were observed in disease-free survival, distant metastases, overall survival, and other endpoints. The approach reduces on-treatment days, improves flexibility in clinical scheduling, and enhances patient convenience, the authors maintained.

“A 2-day adjuvant radiotherapy option allows us to know surgical margin status while still enabling completion of both surgery and radiotherapy in one week or less,” according to Peter Y. Chen, MD, from William Beaumont Hospital in Royal Oak, Michigan.

In another study, investigators from multiple institutions reported on a pooled analysis of 2,127 patients treated at William Beaumont Hospital as part of the American Society of Breast Surgeons MammoSite® Registry Trial.  Patients received adjuvant radiotherapy using either interstitial brachytherapy, balloon-based brachytherapy, or three-dimensional conformal partial-breast irradiation after breast-conserving surgery and were followed a median of 6.6 years.8 They reported excellent outcomes, including a 5-year rate of ipsilateral breast tumor recurrence of 2.5% in “suitable” patients. The researchers further noted that current ASTRO Consensus Statement groups do not adequately differentiate patients at an increased risk of true recurrence at the lumpectomy bed following administration of APBI.

“Given that APBI is increasingly offered to appropriately selected patients outside of a clinical trial as an alternative to whole-breast irradiation, it is encouraging to note that excellent outcomes were seen at 5 years in this combined cohort of patients. These findings support the use of APBI in select individuals with early-stage breast cancer and may be useful in refining the consensus panel guidelines pending long-term follow-up results from phase III trials,” said Ben Wilkinson, MD, lead author of the study who is also from William Beaumont Hospital. ■

Disclosure: Dr. Rugo receives research support (via UCSF) for studies in which she is the principal investigator from Novartis, Pfizer, and Merck. Dr. Brufsky received consulting fees from Genentech-Roche. Drs. Buchholz, Chen, and Wilkinson reported no potential conflicts of interest.

References

1. Arena FP, Noguchi S. Pritchard KI, et al: Everolimus for postmenopausal women with advanced breast cancer: Updated results of the BOLERO-2 phase III trial. 2012 Breast Cancer Symposium. Abstract 99. Presented September 13, 2012.

2. Hart LL, Baselga J, Rugo HS, et al: Effects of everolimus on disease progression in bone and bone markers in patients with bone metastases. 2012 Breast Cancer Symposium. Abstract 102. Presented September 14, 2012.

3. Brufsky A, Hurvitz SA, Perez EA, et al: Final overall survival and safety analyses of RIBBON-2, a randomized phase III trial of bevacizumab vs placebo combined with second-line chemotherapy for HER2-negative bevacizumab-naive metastatic breast cancer. 2012 Breast Cancer Symposium. Abstract 100. Presented September 14, 2012.

4. Staley S-A: Staging evaluation with bone scan, liver ultrasound, and chest radiograph in patients with primary breast cancer: A systematic review. 2012 Breast Cancer Symposium. Abstract 4. Presented September 13, 2012.

5. Wang AT, Fan J, Van Houten HK, et al: Impact of the US Preventive Services task Force update for breast cancer screening on mammography utilization in women age 40 to 49. 2012 Breast Cancer Symposium. Abstract 5. Presented September 13, 2012.

6. Rajapakshe R, Parker B, Araujo C, et al: Stratification of 5-year cancer detection rate in an organized breast screening program based on Gail model risk factors. 2012 Breast Cancer Symposium. Abstract 7. Presented September 13, 2012.

7. Chen PY, Shah C, Wilkinson JB, et al: Clinical efficacy of a 2-day versus 5-day accelerated partial breast irradiation delivered via balloon-based brachytherapy: Results of a matched pair analysis. 2012 Breast Cancer Symposium. Abstract 148. Presented September 13, 2012.

8. Wilkinson JB, Beitsch PD, Arthur DW, et al: Evaluation of current consensus panel guidelines for APBI: A pooled analysis of William Beaumont Hospital and the American Society of Breast Surgeons MammoSite® Registry Trial data. 2012 Breast Cancer Symposium. Abstract 145. Presented September 13, 2012.

9. Skinner KA, Farkas RL, McCarthy K, et al: The surgeon’s impact on ER status. 2012 Breast Cancer Symposium. Abstract 153. Presented September 13, 2012.



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