SABCS 2011

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

The role of bevacizumab has been among the more contentious issues in breast cancer oncology of late. At the San Antonio Breast Cancer Symposium, investigators will add results from two more trials – the BEATRICE and LEA studies – to the ongoing debate.

BEATRICE Targets Early Triple-Negative Disease

Patients had to have confirmed triple-negative disease to be enrolled in the multinational, randomized, open-label BEATRICE study sponsored by Hoffman-La Roche, which markets bevacizumab (Avastin) in Europe.

Their tumors had to be operable primary invasive breast cancer, for which the patients completed definitive locoregional surgery. Those with locally advanced breast cancer were excluded from BEATRICE, which had a target enrollment of more than 2,500 patients.

The underlying question is whether adding 1 year of bevacizumab to standard adjuvant therapy is safe and can improve efficacy. Invasive disease–free survival is the primary outcome measure of BEATRICE, which began recruitment in 2007. "Primary" results are slated for presentation in General Session 6 at the San Antonio meeting (S6-5). Investigators also have prepared a biomarker analysis (Poster session 3, P3-06-34).

LEA Focuses on Advanced Hormone Receptor–Positive Disease

The first efficacy results from the phase III LEA study will focus on the addition of bevacizumab to first-line endocrine treatment in women who are eligible for hormonal therapy and also HER2 negative.

The Spanish Breast Cancer Research Group sponsored the trial in collaboration with the German Breast Group and Hoffmann-La Roche. It was designed to test the hypothesis that targeting the vascular endothelial growth factor (VEGF) with bevacizumab could present resistance to endocrine therapy "in patients with advanced breast cancer sensitive to such treatment" (Cancer Res. 2011;71(24 Supplement):OT3-01-15 [doi: 10.1158/0008-5472.SABCS11-OT3-01-15]).

The protocol called for enrollment of 378 patients with locally advanced or metastatic breast cancer. All received endocrine therapy with letrozole (Femara) or fulvestrant (Faslodex) during the trial; the experimental arm also received bevacizumab, and patients could continue on bevacizumab if they had not progressed on study.

Two-year progression-free survival is the primary end point of the trial, which began recruitment in November 2007. The first efficacy results will be presented in San Antonio (General session 1, S1-7).

Ongoing Quest to Define Who Would Benefit

Just over a year ago, on Nov. 18, 2011, Food and Drug Administration (FDA) Commissioner Margaret Hamburg announced her decision to revoke an indication for bevacizumab in combination with paclitaxel for metastatic breast cancer. She acted after an emotional public hearing at which women with stage IV disease testified that they benefited from bevacizumab.

Earlier, the Oncologic Drugs Advisory Committee (ODAC) had voted unanimously in favor of withdrawal, citing toxicity and noting that confirmatory trials had not repeated the magnitude of benefit in the E2100 trial (J. Clin. Oncol. 2009;27:4966-72) on which accelerated approval had been based.

The National Comprehensive Cancer Network (NCCN) has stood by its endorsement of bevacizumab in combination with paclitaxel, however. "The data observed in the [E2100 trial] really had not changed from its approval previously, and we thought that if the data were compelling 2 years ago, why isn’t it compelling enough today?" explained Dr. Robert W. Carlson of Stanford (Calif.) University, chair of the NCCN’s breast cancer panel, after the FDA moved to revoke the indication.

Genentech, the U.S. drugmaker owned by Roche, expressed disappointment with the final FDA decision, and vowed to continue seeking biomarkers that would identify which breast cancer patients can benefit from bevacizumab.

This fall, investigators presented results of the Roche-sponsored TURANDOT trial at the annual meeting of the European Society for Medical Oncology in Vienna. They reported that paclitaxel appeared to be a better partner than capecitabine (Xeloda) for bevacizumab in patients with metastatic breast cancer, but overall survival was not significantly different between the two combinations, and results echoed outcomes in earlier trials.

Quality-of-life results from the TURANDOT trial will be presented in a poster session in San Antonio (Poster session, P5-17-03). Among the other scheduled bevacizumab presentations are:

• Final results of the single-arm, phase II AVANTHER trial from Spain. Investigators combined bevacizumab and trastuzumab (Herceptin) with weekly paclitaxel as a neoadjuvant treatment in HER2-positive breast cancer. Treatment was followed by surgery and adjuvant therapy (Poster session 1, P1-14-10).

• First toxicity results from the Eastern Cooperative Oncology Group E5103 trial. This randomized phase III study compared doxorubicin, cyclophosphamide, and paclitaxel with and without bevacizumab in patients with lymph node–positive or high-risk, lymph node–negative breast cancer (Poster session 5, P5-17-01).

Cancer care has emerged as a prime target in efforts to contain health care costs.

Health policy makers have painted a bull’s-eye on oncology. Cancer therapy costs are skyrocketing, and the care itself is sometimes seen as fragmented and unsupported by persuasive evidence of effectiveness.

Moreover, cost hasn’t typically been a consideration for American oncologists. The prevailing ethos has been that they have a duty to offer a patient any possible treatment yielding a net benefit, regardless of the cost to society.

© Kativ / iStockphoto.com

That stance is no longer tenable, experts said in interviews and presentations at the recent San Antonio Breast Cancer Symposium.

"The growth in health care spending is unsustainable. Like it or not, efforts to control costs will increase. The question isn’t ‘Should cost be a consideration in the management of cancer?’ but rather ‘How will cost decisions be made and who will be responsible?’ " said Dr. Michael J. Hassett, a medical oncologist at the Dana-Farber Cancer Institute and Harvard Medical School, Boston.

Dr. Thomas J. Smith, the Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore, concurred.

"I’ve just spent the past couple of days talking to major insurers about the new Medicare/Medicaid innovations program, and everyone says oncology is a major target," said Dr. Smith, director of palliative care at Johns Hopkins Medicine. "It’s 15%-25% of their insurance costs. And there are demonstration projects showing that episode-based payment and salaried physicians work just as well and cost less."

The Association of American Medical Colleges plans to make "cost-conscious use of society’s resources" the next scientific competency required of medical school graduates, added Dr. Smith. "So we’re going to have to figure this out and teach it to the next generation, even if we ourselves didn’t get it right."

A defining experience for Dr. Eric P. Winer came when he and other international experts met in Portugal to draw up consensus guidelines on the treatment of advanced breast cancer.

"It was a surprising moment that seems to keep coming back to me over and over again: Many of our European colleagues were quite open in saying that newer drugs that might lead to a fairly modest survival advantage would probably not be used in their countries if the drugs were costly," recalled Dr. Winer, director of the breast oncology center at Dana-Farber and a professor of medicine at Harvard.

"That’s very different from the approach taken in the [United States] until now, although I think we’re really looking to make changes here," he said. "My own view is, if we don’t take control of this as the people who are providing care, then we will lose all control."

Yet if clinicians are to assume responsibility for considering costs in making cancer treatment decisions, they will have to traverse an ethical mine field, given their multiple potentially conflicting responsibilities as patient advocates, business owners, and citizen-taxpayers, cautioned Dr. Hassett.

Money and Outcomes Don’t Match

In 2009, nearly 18% of the U.S. gross domestic product was spent on health care. Analysts at the National Cancer Institute estimate that direct medical spending on cancer care in the U.S. amounted to $124.5 billion in 2010, with breast cancer care – accounting for $16.5 billion, or 13% of the total – leading the way. By 2020, just 8 years from now, they project that direct medical spending for cancer care will approach $158 billion annually, with breast cancer accounting for up to $25 billion of that figure (Cancer Epidemiol. Biomarkers Prev. 2011;20:2006-14).

How is that money being spent? A separate study concluded that total Medicare fee-for-service spending for breast cancer care during the initial year after diagnosis amounted to $1.06 billion in 2002. Surgery accounted for 25% of that payout, followed by chemotherapy at 15%, radiation therapy at 11%, and other inpatient care at 18% (J. Natl. Cancer Inst. 2008;100:888-97).

Unfortunately, all that spending isn’t buying better outcomes. By a variety of yardsticks, including 5-year overall survival and potential years of life lost due to malignancy, Americans fare no better and in some cases do worse than citizens of countries spending far less per capita on health care, said Dr. Hassett.

In a soon-to-be-published study, he and his coinvestigators analyzed total per-patient expenditures for all Medicare Part A and Part B services for breast cancer during the year following diagnosis of the malignancy in more than 15,000 women aged 65-70 years. Patients in the lowest quintile, with a median 1-year spending of $17,315, had a 5-year overall survival of 88%, identical to that in women in the highest spending quintile, at $26,808. Both quintiles had an identical 81% rate of adherence to 27 National Comprehensive Cancer Network guideline-based quality measures.

How Much Is Too Much per QALY?

Incremental cost-effectiveness analysis is an increasingly popular tool for helping determine whether an intervention provides value for money spent, according to Elena B. Elkin, Ph.D., of the Health Outcomes Research Group at Memorial Sloan-Kettering Cancer Center, New York.

For example, breast cancer cost-effectiveness studies published in recent years have concluded that the use of raloxifene (Evista) to reduce breast cancer risk among white women starting at age 55 comes at a price tag of $22,000 per quality-adjusted life year (QALY) gained. Similarly, the use of adjuvant letrozole (Femara) instead of anastrozole (Arimidex) in patients with hormone receptor–positive breast cancer has a cost of $26,000 per QALY.

At the higher end of the spectrum, bevacizumab (Avastin) plus paclitaxel vs. paclitaxel alone in women with HER2-positive metastatic breast cancer has a cost-effectiveness of $280,000 per QALY; ixabepilone (Ixempra) plus capecitabine (Xeloda) vs. capecitabine alone in the setting of taxane- and anthracycline-resistant metastatic breast cancer has been calculated to carry a price tag of $360,000 per QALY; and digital screening mammography instead of film for all women aged 40 or older costs an estimated $930,000 per QALY gained, according to Dr. Elkin.

There is no "right" answer as to what constitutes good value for money spent on health care. A widespread view held since the early 1980s is that less than $50,000 per QALY is a favorably low incremental cost-effectiveness ratio and thus good value, whereas $50,000-$100,000 per QALY is a grey area and a judgment call. But those rules of thumb are "certainly outdated," said Dr. Elkin.

She noted that Dr. Smith and Dr. Bruce E. Hillner have calculated that by adjusting for health care inflation, an incremental cost-effectiveness ratio of $50,000 per QALY in 1982 equates to $197,000 per QALY in 2007 dollars. Moreover, using the World Health Organization definition of good value for health care money spent (that is, a figure not more than three times a nation’s per capita gross domestic product), then $140,100 per QALY in 2008 U.S. dollars would be a reasonable threshold (J. Clin. Oncol. 2009;27:2111-3).

Impact on Care Worries Oncologists

There are indications that many oncologists are concerned about the exponentially rising cost of cancer care but leery about the possible unintended consequences of efforts to control costs, such as jeopardizing quality or access.

A national survey of medical oncologists conducted by researchers at Tufts University showed that 84% said that patients’ out-of-pocket costs influence their treatment recommendations. Some 56% indicated the cost of new cancer drugs influences their treatment recommendations. Only 29% believe that more cost-sharing by patients for cancer drugs is needed. And 80% of those surveyed want to see more use of cost-effectiveness data in coverage and payment decisions (Health Aff. [Millwood] 2010;29:196-202).

When asked who should determine whether a drug provides good value, 60% of the medical oncologists responded that physicians should make this determination; 57% said nonprofit organizations, 37% said patients, 21% named the government, and 6% said insurance companies.

"I think that’s interesting, because in reality it’s probably the reverse of what actually happens," according to Dr. Hassett.

Earlier Adoption of Trial Results Urged

Dr. Laura J. Esserman suggested that one novel way to curb cancer care costs is through selective early adoption of persuasive clinical trial findings while ongoing definitive studies are still being completed. She cited intraoperative radiation therapy during breast-conserving surgery as a case in point.

Results of the international TARGIT-A (Targeted Intraoperative Radiotherapy) trial, in which 2,232 patients undergoing lumpectomy were randomized to intraoperative radiotherapy (IORT) or standard external-beam radiation, showed closely similar 4-year local recurrence rates in the conserved breast: 1.2% in the IORT group and 0.95% with external-beam radiation (Lancet 2010;376:91-102). Yet IORT costs $6,400 less and provides enormous quality of life advantages, as it replaces the conventional 6 weeks of near-daily radiation therapy with 30 minutes of intraoperative treatment.

"To wake up from your surgery and be done is a wonderful thing," commented Dr. Esserman, professor of surgery and radiology and director of the breast care center at the University of California, San Francisco.

More than 70,000 American women per year who have been diagnosed with breast cancer fit the profile of the TARGIT-A population, she said. Yet some authorities urge holding off on widespread adoption of IORT until results are in from ongoing, large, randomized trials of mastectomy vs. lumpectomy and various forms of radiation, which will take another decade or more.

"The possible harm of early adoption is negligible, and the cost of not intervening is close to $2 billion per year. I strongly feel IORT should be adopted now. I don’t think the results are going to change. We’ve already adopted it at our center, and a registry trial is being organized to help people adopt it nationally," said Dr. Esserman.

A major obstacle here is Medicare’s decision to make IORT part of a bundled-care program, which means that physicians who perform radiation therapy intraoperatively won’t get paid more for it. "This will provide an enormous disincentive to the use of IORT. The big losers here are the patients," she said.

Another opportunity to save money would be to follow the U.S. Preventive Services Task Force guidelines on mammography screening for breast cancer, rather than routinely conducting annual mammography, as many physicians still advocate, Dr. Esserman continued.

"We could save $5 billion per year simply by following those guidelines. And there are now many papers demonstrating that approach certainly is very cost effective. You don’t find any significant increase in advanced cancers with annual screening," she said.

Five More Proposals to Slow Costs

Dr. Smith proposed the following five changes in oncologists’ behavior aimed at slowing the rise in cancer care costs:

• Target surveillance testing with serum tumor markers and imaging in accord with NCCN guidelines. Recommendations to cut back on surveillance testing ought to be incorporated into the American Society of Clinical Oncology’s Quality Oncology Practice Initiative (QOPI), a program of proven effectiveness in changing medical oncologists’ behavior.

• Switch to palliative care in patients with disease progression despite three consecutive chemotherapy regimens. The US Oncology Network’s pathway for metastatic non–small cell lung cancer, which takes this approach, has been shown to reduce treatment costs by 35% with exactly the same survival as in patients treated off pathway – and with better quality of life stemming from a doubled length of stay in hospice care (J. Oncol. Pract. 2010;6:12-18). The same research group reported that a similarly structured pathway for metastatic colon cancer led to a reduction in treatment costs by one-third, along with a significant 6.8-month improvement in survival compared with off-pathway treatment (Am. J. Manag. Care 2011;May [suppl. 5 Developing]: SP45-52).

• Limit chemotherapy for most patients with advanced metastatic solid tumors to patients with good performance status. This would markedly decrease the use of chemotherapy at the end of life.

• Substitute a reduction in chemotherapy dose for the current routine use of colony-stimulating factors in patients with metastatic solid cancers. "We are 3% of the world’s population and we use 75% of the world’s colony-stimulating factors. And 90% of that use isn’t supported by ASCO guidelines," the oncologist asserted. "I think that’s going to be a big target going forward. We simply can’t afford $3,500 per injection for a drug that helps with supportive care but doesn’t improve survival."

• Sequential monotherapies rather than combination chemotherapies as second- and third-line treatment for metastatic cancer. The available data suggest patients will live just as long, but with fewer toxic effects – and at lower cost.

Personalized Medicine and Palliative Care

Dr. Hassett cautioned that although conventional wisdom holds that the emerging field of "personalized medicine" will favorably impact health care costs by providing more selective therapy and improved clinical outcomes, that’s by no means a slam dunk.

"I’m just not sure. I think there’s a chance that personalized medicine could actually increase costs by introducing more expensive tests, new and more expensive drugs, and more complexity into the system," he said.

One thing he is sure of, however, is that any successful effort to reduce the rate of growth in cancer care spending will necessarily have to address the hot-button issue of end-of-life care. One-tenth of all Medicare dollars are spent on care during the final 28 days of life.

Dr. Smith concurred, adding that ASCO has a soon-to-be-published Provisional Clinical Opinion declaring that all oncologists should integrate palliative care into their usual cancer care programs.

"That should be the norm. We have to look at how we spend that money for end-of-life [care] because if we don’t fix that part, we won’t have money for adjuvant therapy and neoadjuvant therapy and funding for major research," he warned.

None of the experts cited in this article declared having any financial conflicts.

Cancer care has emerged as a prime target in efforts to contain health care costs.

Health policy makers have painted a bull’s-eye on oncology. Cancer therapy costs are skyrocketing, and the care itself is sometimes seen as fragmented and unsupported by persuasive evidence of effectiveness.

Moreover, cost hasn’t typically been a consideration for American oncologists. The prevailing ethos has been that they have a duty to offer a patient any possible treatment yielding a net benefit, regardless of the cost to society.

© Kativ / iStockphoto.com

That stance is no longer tenable, experts said in interviews and presentations at the recent San Antonio Breast Cancer Symposium.

"The growth in health care spending is unsustainable. Like it or not, efforts to control costs will increase. The question isn’t ‘Should cost be a consideration in the management of cancer?’ but rather ‘How will cost decisions be made and who will be responsible?’ " said Dr. Michael J. Hassett, a medical oncologist at the Dana-Farber Cancer Institute and Harvard Medical School, Boston.

Dr. Thomas J. Smith, the Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore, concurred.

"I’ve just spent the past couple of days talking to major insurers about the new Medicare/Medicaid innovations program, and everyone says oncology is a major target," said Dr. Smith, director of palliative care at Johns Hopkins Medicine. "It’s 15%-25% of their insurance costs. And there are demonstration projects showing that episode-based payment and salaried physicians work just as well and cost less."

The Association of American Medical Colleges plans to make "cost-conscious use of society’s resources" the next scientific competency required of medical school graduates, added Dr. Smith. "So we’re going to have to figure this out and teach it to the next generation, even if we ourselves didn’t get it right."

A defining experience for Dr. Eric P. Winer came when he and other international experts met in Portugal to draw up consensus guidelines on the treatment of advanced breast cancer.

"It was a surprising moment that seems to keep coming back to me over and over again: Many of our European colleagues were quite open in saying that newer drugs that might lead to a fairly modest survival advantage would probably not be used in their countries if the drugs were costly," recalled Dr. Winer, director of the breast oncology center at Dana-Farber and a professor of medicine at Harvard.

"That’s very different from the approach taken in the [United States] until now, although I think we’re really looking to make changes here," he said. "My own view is, if we don’t take control of this as the people who are providing care, then we will lose all control."

Yet if clinicians are to assume responsibility for considering costs in making cancer treatment decisions, they will have to traverse an ethical mine field, given their multiple potentially conflicting responsibilities as patient advocates, business owners, and citizen-taxpayers, cautioned Dr. Hassett.

Money and Outcomes Don’t Match

In 2009, nearly 18% of the U.S. gross domestic product was spent on health care. Analysts at the National Cancer Institute estimate that direct medical spending on cancer care in the U.S. amounted to $124.5 billion in 2010, with breast cancer care – accounting for $16.5 billion, or 13% of the total – leading the way. By 2020, just 8 years from now, they project that direct medical spending for cancer care will approach $158 billion annually, with breast cancer accounting for up to $25 billion of that figure (Cancer Epidemiol. Biomarkers Prev. 2011;20:2006-14).

How is that money being spent? A separate study concluded that total Medicare fee-for-service spending for breast cancer care during the initial year after diagnosis amounted to $1.06 billion in 2002. Surgery accounted for 25% of that payout, followed by chemotherapy at 15%, radiation therapy at 11%, and other inpatient care at 18% (J. Natl. Cancer Inst. 2008;100:888-97).

Unfortunately, all that spending isn’t buying better outcomes. By a variety of yardsticks, including 5-year overall survival and potential years of life lost due to malignancy, Americans fare no better and in some cases do worse than citizens of countries spending far less per capita on health care, said Dr. Hassett.

In a soon-to-be-published study, he and his coinvestigators analyzed total per-patient expenditures for all Medicare Part A and Part B services for breast cancer during the year following diagnosis of the malignancy in more than 15,000 women aged 65-70 years. Patients in the lowest quintile, with a median 1-year spending of $17,315, had a 5-year overall survival of 88%, identical to that in women in the highest spending quintile, at $26,808. Both quintiles had an identical 81% rate of adherence to 27 National Comprehensive Cancer Network guideline-based quality measures.

How Much Is Too Much per QALY?

Incremental cost-effectiveness analysis is an increasingly popular tool for helping determine whether an intervention provides value for money spent, according to Elena B. Elkin, Ph.D., of the Health Outcomes Research Group at Memorial Sloan-Kettering Cancer Center, New York.

For example, breast cancer cost-effectiveness studies published in recent years have concluded that the use of raloxifene (Evista) to reduce breast cancer risk among white women starting at age 55 comes at a price tag of $22,000 per quality-adjusted life year (QALY) gained. Similarly, the use of adjuvant letrozole (Femara) instead of anastrozole (Arimidex) in patients with hormone receptor–positive breast cancer has a cost of $26,000 per QALY.

At the higher end of the spectrum, bevacizumab (Avastin) plus paclitaxel vs. paclitaxel alone in women with HER2-positive metastatic breast cancer has a cost-effectiveness of $280,000 per QALY; ixabepilone (Ixempra) plus capecitabine (Xeloda) vs. capecitabine alone in the setting of taxane- and anthracycline-resistant metastatic breast cancer has been calculated to carry a price tag of $360,000 per QALY; and digital screening mammography instead of film for all women aged 40 or older costs an estimated $930,000 per QALY gained, according to Dr. Elkin.

There is no "right" answer as to what constitutes good value for money spent on health care. A widespread view held since the early 1980s is that less than $50,000 per QALY is a favorably low incremental cost-effectiveness ratio and thus good value, whereas $50,000-$100,000 per QALY is a grey area and a judgment call. But those rules of thumb are "certainly outdated," said Dr. Elkin.

She noted that Dr. Smith and Dr. Bruce E. Hillner have calculated that by adjusting for health care inflation, an incremental cost-effectiveness ratio of $50,000 per QALY in 1982 equates to $197,000 per QALY in 2007 dollars. Moreover, using the World Health Organization definition of good value for health care money spent (that is, a figure not more than three times a nation’s per capita gross domestic product), then $140,100 per QALY in 2008 U.S. dollars would be a reasonable threshold (J. Clin. Oncol. 2009;27:2111-3).

Impact on Care Worries Oncologists

There are indications that many oncologists are concerned about the exponentially rising cost of cancer care but leery about the possible unintended consequences of efforts to control costs, such as jeopardizing quality or access.

A national survey of medical oncologists conducted by researchers at Tufts University showed that 84% said that patients’ out-of-pocket costs influence their treatment recommendations. Some 56% indicated the cost of new cancer drugs influences their treatment recommendations. Only 29% believe that more cost-sharing by patients for cancer drugs is needed. And 80% of those surveyed want to see more use of cost-effectiveness data in coverage and payment decisions (Health Aff. [Millwood] 2010;29:196-202).

When asked who should determine whether a drug provides good value, 60% of the medical oncologists responded that physicians should make this determination; 57% said nonprofit organizations, 37% said patients, 21% named the government, and 6% said insurance companies.

"I think that’s interesting, because in reality it’s probably the reverse of what actually happens," according to Dr. Hassett.

Earlier Adoption of Trial Results Urged

Dr. Laura J. Esserman suggested that one novel way to curb cancer care costs is through selective early adoption of persuasive clinical trial findings while ongoing definitive studies are still being completed. She cited intraoperative radiation therapy during breast-conserving surgery as a case in point.

Results of the international TARGIT-A (Targeted Intraoperative Radiotherapy) trial, in which 2,232 patients undergoing lumpectomy were randomized to intraoperative radiotherapy (IORT) or standard external-beam radiation, showed closely similar 4-year local recurrence rates in the conserved breast: 1.2% in the IORT group and 0.95% with external-beam radiation (Lancet 2010;376:91-102). Yet IORT costs $6,400 less and provides enormous quality of life advantages, as it replaces the conventional 6 weeks of near-daily radiation therapy with 30 minutes of intraoperative treatment.

"To wake up from your surgery and be done is a wonderful thing," commented Dr. Esserman, professor of surgery and radiology and director of the breast care center at the University of California, San Francisco.

More than 70,000 American women per year who have been diagnosed with breast cancer fit the profile of the TARGIT-A population, she said. Yet some authorities urge holding off on widespread adoption of IORT until results are in from ongoing, large, randomized trials of mastectomy vs. lumpectomy and various forms of radiation, which will take another decade or more.

"The possible harm of early adoption is negligible, and the cost of not intervening is close to $2 billion per year. I strongly feel IORT should be adopted now. I don’t think the results are going to change. We’ve already adopted it at our center, and a registry trial is being organized to help people adopt it nationally," said Dr. Esserman.

A major obstacle here is Medicare’s decision to make IORT part of a bundled-care program, which means that physicians who perform radiation therapy intraoperatively won’t get paid more for it. "This will provide an enormous disincentive to the use of IORT. The big losers here are the patients," she said.

Another opportunity to save money would be to follow the U.S. Preventive Services Task Force guidelines on mammography screening for breast cancer, rather than routinely conducting annual mammography, as many physicians still advocate, Dr. Esserman continued.

"We could save $5 billion per year simply by following those guidelines. And there are now many papers demonstrating that approach certainly is very cost effective. You don’t find any significant increase in advanced cancers with annual screening," she said.

Five More Proposals to Slow Costs

Dr. Smith proposed the following five changes in oncologists’ behavior aimed at slowing the rise in cancer care costs:

• Target surveillance testing with serum tumor markers and imaging in accord with NCCN guidelines. Recommendations to cut back on surveillance testing ought to be incorporated into the American Society of Clinical Oncology’s Quality Oncology Practice Initiative (QOPI), a program of proven effectiveness in changing medical oncologists’ behavior.

• Switch to palliative care in patients with disease progression despite three consecutive chemotherapy regimens. The US Oncology Network’s pathway for metastatic non–small cell lung cancer, which takes this approach, has been shown to reduce treatment costs by 35% with exactly the same survival as in patients treated off pathway – and with better quality of life stemming from a doubled length of stay in hospice care (J. Oncol. Pract. 2010;6:12-18). The same research group reported that a similarly structured pathway for metastatic colon cancer led to a reduction in treatment costs by one-third, along with a significant 6.8-month improvement in survival compared with off-pathway treatment (Am. J. Manag. Care 2011;May [suppl. 5 Developing]: SP45-52).

• Limit chemotherapy for most patients with advanced metastatic solid tumors to patients with good performance status. This would markedly decrease the use of chemotherapy at the end of life.

• Substitute a reduction in chemotherapy dose for the current routine use of colony-stimulating factors in patients with metastatic solid cancers. "We are 3% of the world’s population and we use 75% of the world’s colony-stimulating factors. And 90% of that use isn’t supported by ASCO guidelines," the oncologist asserted. "I think that’s going to be a big target going forward. We simply can’t afford $3,500 per injection for a drug that helps with supportive care but doesn’t improve survival."

• Sequential monotherapies rather than combination chemotherapies as second- and third-line treatment for metastatic cancer. The available data suggest patients will live just as long, but with fewer toxic effects – and at lower cost.

Personalized Medicine and Palliative Care

Dr. Hassett cautioned that although conventional wisdom holds that the emerging field of "personalized medicine" will favorably impact health care costs by providing more selective therapy and improved clinical outcomes, that’s by no means a slam dunk.

"I’m just not sure. I think there’s a chance that personalized medicine could actually increase costs by introducing more expensive tests, new and more expensive drugs, and more complexity into the system," he said.

One thing he is sure of, however, is that any successful effort to reduce the rate of growth in cancer care spending will necessarily have to address the hot-button issue of end-of-life care. One-tenth of all Medicare dollars are spent on care during the final 28 days of life.

Dr. Smith concurred, adding that ASCO has a soon-to-be-published Provisional Clinical Opinion declaring that all oncologists should integrate palliative care into their usual cancer care programs.

"That should be the norm. We have to look at how we spend that money for end-of-life [care] because if we don’t fix that part, we won’t have money for adjuvant therapy and neoadjuvant therapy and funding for major research," he warned.

None of the experts cited in this article declared having any financial conflicts.

Cancer care has emerged as a prime target in efforts to contain health care costs.

Health policy makers have painted a bull’s-eye on oncology. Cancer therapy costs are skyrocketing, and the care itself is sometimes seen as fragmented and unsupported by persuasive evidence of effectiveness.

Moreover, cost hasn’t typically been a consideration for American oncologists. The prevailing ethos has been that they have a duty to offer a patient any possible treatment yielding a net benefit, regardless of the cost to society.

© Kativ / iStockphoto.com

That stance is no longer tenable, experts said in interviews and presentations at the recent San Antonio Breast Cancer Symposium.

"The growth in health care spending is unsustainable. Like it or not, efforts to control costs will increase. The question isn’t ‘Should cost be a consideration in the management of cancer?’ but rather ‘How will cost decisions be made and who will be responsible?’ " said Dr. Michael J. Hassett, a medical oncologist at the Dana-Farber Cancer Institute and Harvard Medical School, Boston.

Dr. Thomas J. Smith, the Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore, concurred.

"I’ve just spent the past couple of days talking to major insurers about the new Medicare/Medicaid innovations program, and everyone says oncology is a major target," said Dr. Smith, director of palliative care at Johns Hopkins Medicine. "It’s 15%-25% of their insurance costs. And there are demonstration projects showing that episode-based payment and salaried physicians work just as well and cost less."

The Association of American Medical Colleges plans to make "cost-conscious use of society’s resources" the next scientific competency required of medical school graduates, added Dr. Smith. "So we’re going to have to figure this out and teach it to the next generation, even if we ourselves didn’t get it right."

A defining experience for Dr. Eric P. Winer came when he and other international experts met in Portugal to draw up consensus guidelines on the treatment of advanced breast cancer.

"It was a surprising moment that seems to keep coming back to me over and over again: Many of our European colleagues were quite open in saying that newer drugs that might lead to a fairly modest survival advantage would probably not be used in their countries if the drugs were costly," recalled Dr. Winer, director of the breast oncology center at Dana-Farber and a professor of medicine at Harvard.

"That’s very different from the approach taken in the [United States] until now, although I think we’re really looking to make changes here," he said. "My own view is, if we don’t take control of this as the people who are providing care, then we will lose all control."

Yet if clinicians are to assume responsibility for considering costs in making cancer treatment decisions, they will have to traverse an ethical mine field, given their multiple potentially conflicting responsibilities as patient advocates, business owners, and citizen-taxpayers, cautioned Dr. Hassett.

Money and Outcomes Don’t Match

In 2009, nearly 18% of the U.S. gross domestic product was spent on health care. Analysts at the National Cancer Institute estimate that direct medical spending on cancer care in the U.S. amounted to $124.5 billion in 2010, with breast cancer care – accounting for $16.5 billion, or 13% of the total – leading the way. By 2020, just 8 years from now, they project that direct medical spending for cancer care will approach $158 billion annually, with breast cancer accounting for up to $25 billion of that figure (Cancer Epidemiol. Biomarkers Prev. 2011;20:2006-14).

How is that money being spent? A separate study concluded that total Medicare fee-for-service spending for breast cancer care during the initial year after diagnosis amounted to $1.06 billion in 2002. Surgery accounted for 25% of that payout, followed by chemotherapy at 15%, radiation therapy at 11%, and other inpatient care at 18% (J. Natl. Cancer Inst. 2008;100:888-97).

Unfortunately, all that spending isn’t buying better outcomes. By a variety of yardsticks, including 5-year overall survival and potential years of life lost due to malignancy, Americans fare no better and in some cases do worse than citizens of countries spending far less per capita on health care, said Dr. Hassett.

In a soon-to-be-published study, he and his coinvestigators analyzed total per-patient expenditures for all Medicare Part A and Part B services for breast cancer during the year following diagnosis of the malignancy in more than 15,000 women aged 65-70 years. Patients in the lowest quintile, with a median 1-year spending of $17,315, had a 5-year overall survival of 88%, identical to that in women in the highest spending quintile, at $26,808. Both quintiles had an identical 81% rate of adherence to 27 National Comprehensive Cancer Network guideline-based quality measures.

How Much Is Too Much per QALY?

Incremental cost-effectiveness analysis is an increasingly popular tool for helping determine whether an intervention provides value for money spent, according to Elena B. Elkin, Ph.D., of the Health Outcomes Research Group at Memorial Sloan-Kettering Cancer Center, New York.

For example, breast cancer cost-effectiveness studies published in recent years have concluded that the use of raloxifene (Evista) to reduce breast cancer risk among white women starting at age 55 comes at a price tag of $22,000 per quality-adjusted life year (QALY) gained. Similarly, the use of adjuvant letrozole (Femara) instead of anastrozole (Arimidex) in patients with hormone receptor–positive breast cancer has a cost of $26,000 per QALY.

At the higher end of the spectrum, bevacizumab (Avastin) plus paclitaxel vs. paclitaxel alone in women with HER2-positive metastatic breast cancer has a cost-effectiveness of $280,000 per QALY; ixabepilone (Ixempra) plus capecitabine (Xeloda) vs. capecitabine alone in the setting of taxane- and anthracycline-resistant metastatic breast cancer has been calculated to carry a price tag of $360,000 per QALY; and digital screening mammography instead of film for all women aged 40 or older costs an estimated $930,000 per QALY gained, according to Dr. Elkin.

There is no "right" answer as to what constitutes good value for money spent on health care. A widespread view held since the early 1980s is that less than $50,000 per QALY is a favorably low incremental cost-effectiveness ratio and thus good value, whereas $50,000-$100,000 per QALY is a grey area and a judgment call. But those rules of thumb are "certainly outdated," said Dr. Elkin.

She noted that Dr. Smith and Dr. Bruce E. Hillner have calculated that by adjusting for health care inflation, an incremental cost-effectiveness ratio of $50,000 per QALY in 1982 equates to $197,000 per QALY in 2007 dollars. Moreover, using the World Health Organization definition of good value for health care money spent (that is, a figure not more than three times a nation’s per capita gross domestic product), then $140,100 per QALY in 2008 U.S. dollars would be a reasonable threshold (J. Clin. Oncol. 2009;27:2111-3).

Impact on Care Worries Oncologists

There are indications that many oncologists are concerned about the exponentially rising cost of cancer care but leery about the possible unintended consequences of efforts to control costs, such as jeopardizing quality or access.

A national survey of medical oncologists conducted by researchers at Tufts University showed that 84% said that patients’ out-of-pocket costs influence their treatment recommendations. Some 56% indicated the cost of new cancer drugs influences their treatment recommendations. Only 29% believe that more cost-sharing by patients for cancer drugs is needed. And 80% of those surveyed want to see more use of cost-effectiveness data in coverage and payment decisions (Health Aff. [Millwood] 2010;29:196-202).

When asked who should determine whether a drug provides good value, 60% of the medical oncologists responded that physicians should make this determination; 57% said nonprofit organizations, 37% said patients, 21% named the government, and 6% said insurance companies.

"I think that’s interesting, because in reality it’s probably the reverse of what actually happens," according to Dr. Hassett.

Earlier Adoption of Trial Results Urged

Dr. Laura J. Esserman suggested that one novel way to curb cancer care costs is through selective early adoption of persuasive clinical trial findings while ongoing definitive studies are still being completed. She cited intraoperative radiation therapy during breast-conserving surgery as a case in point.

Results of the international TARGIT-A (Targeted Intraoperative Radiotherapy) trial, in which 2,232 patients undergoing lumpectomy were randomized to intraoperative radiotherapy (IORT) or standard external-beam radiation, showed closely similar 4-year local recurrence rates in the conserved breast: 1.2% in the IORT group and 0.95% with external-beam radiation (Lancet 2010;376:91-102). Yet IORT costs $6,400 less and provides enormous quality of life advantages, as it replaces the conventional 6 weeks of near-daily radiation therapy with 30 minutes of intraoperative treatment.

"To wake up from your surgery and be done is a wonderful thing," commented Dr. Esserman, professor of surgery and radiology and director of the breast care center at the University of California, San Francisco.

More than 70,000 American women per year who have been diagnosed with breast cancer fit the profile of the TARGIT-A population, she said. Yet some authorities urge holding off on widespread adoption of IORT until results are in from ongoing, large, randomized trials of mastectomy vs. lumpectomy and various forms of radiation, which will take another decade or more.

"The possible harm of early adoption is negligible, and the cost of not intervening is close to $2 billion per year. I strongly feel IORT should be adopted now. I don’t think the results are going to change. We’ve already adopted it at our center, and a registry trial is being organized to help people adopt it nationally," said Dr. Esserman.

A major obstacle here is Medicare’s decision to make IORT part of a bundled-care program, which means that physicians who perform radiation therapy intraoperatively won’t get paid more for it. "This will provide an enormous disincentive to the use of IORT. The big losers here are the patients," she said.

Another opportunity to save money would be to follow the U.S. Preventive Services Task Force guidelines on mammography screening for breast cancer, rather than routinely conducting annual mammography, as many physicians still advocate, Dr. Esserman continued.

"We could save $5 billion per year simply by following those guidelines. And there are now many papers demonstrating that approach certainly is very cost effective. You don’t find any significant increase in advanced cancers with annual screening," she said.

Five More Proposals to Slow Costs

Dr. Smith proposed the following five changes in oncologists’ behavior aimed at slowing the rise in cancer care costs:

• Target surveillance testing with serum tumor markers and imaging in accord with NCCN guidelines. Recommendations to cut back on surveillance testing ought to be incorporated into the American Society of Clinical Oncology’s Quality Oncology Practice Initiative (QOPI), a program of proven effectiveness in changing medical oncologists’ behavior.

• Switch to palliative care in patients with disease progression despite three consecutive chemotherapy regimens. The US Oncology Network’s pathway for metastatic non–small cell lung cancer, which takes this approach, has been shown to reduce treatment costs by 35% with exactly the same survival as in patients treated off pathway – and with better quality of life stemming from a doubled length of stay in hospice care (J. Oncol. Pract. 2010;6:12-18). The same research group reported that a similarly structured pathway for metastatic colon cancer led to a reduction in treatment costs by one-third, along with a significant 6.8-month improvement in survival compared with off-pathway treatment (Am. J. Manag. Care 2011;May [suppl. 5 Developing]: SP45-52).

• Limit chemotherapy for most patients with advanced metastatic solid tumors to patients with good performance status. This would markedly decrease the use of chemotherapy at the end of life.

• Substitute a reduction in chemotherapy dose for the current routine use of colony-stimulating factors in patients with metastatic solid cancers. "We are 3% of the world’s population and we use 75% of the world’s colony-stimulating factors. And 90% of that use isn’t supported by ASCO guidelines," the oncologist asserted. "I think that’s going to be a big target going forward. We simply can’t afford $3,500 per injection for a drug that helps with supportive care but doesn’t improve survival."

• Sequential monotherapies rather than combination chemotherapies as second- and third-line treatment for metastatic cancer. The available data suggest patients will live just as long, but with fewer toxic effects – and at lower cost.

Personalized Medicine and Palliative Care

Dr. Hassett cautioned that although conventional wisdom holds that the emerging field of "personalized medicine" will favorably impact health care costs by providing more selective therapy and improved clinical outcomes, that’s by no means a slam dunk.

"I’m just not sure. I think there’s a chance that personalized medicine could actually increase costs by introducing more expensive tests, new and more expensive drugs, and more complexity into the system," he said.

One thing he is sure of, however, is that any successful effort to reduce the rate of growth in cancer care spending will necessarily have to address the hot-button issue of end-of-life care. One-tenth of all Medicare dollars are spent on care during the final 28 days of life.

Dr. Smith concurred, adding that ASCO has a soon-to-be-published Provisional Clinical Opinion declaring that all oncologists should integrate palliative care into their usual cancer care programs.

"That should be the norm. We have to look at how we spend that money for end-of-life [care] because if we don’t fix that part, we won’t have money for adjuvant therapy and neoadjuvant therapy and funding for major research," he warned.

None of the experts cited in this article declared having any financial conflicts.

SAN ANTONIO – Total skin-sparing mastectomy with complete preservation of the breast skin envelope was associated with favorable oncologic and ischemic outcomes in a large, high-risk cohort of women who underwent the procedure over a 10-year period in San Francisco, a study has shown.

The findings suggest that the surgery, which produces superior cosmesis and is associated with a high rate of patient satisfaction, is a reasonable option for many women facing therapeutic or prophylactic mastectomy, Dr. Anne G. Warren Peled said at the San Antonio Breast Cancer Symposium.

The total skin-sparing mastectomy (TSSM) allows preservation of the nipple-areola dermal layer when ductal tissue is removed during mastectomy. "The procedure is increasingly offered to women for both therapeutic and prophylactic indications, and when combined with immediate breast reconstruction, can produce excellent aesthetic results," explained Dr. Warren Peled, a surgical resident at the University of California, San Francisco.

Because the oncologic safety of the procedure and the potential for higher rates of postoperative complications continue to be debated, Dr. Warren Peled and her colleagues sought to evaluate both outcomes using data collected in a prospectively maintained database. The investigators analyzed patient and tumor characteristics, treatment details, and the development of any postoperative complications, as well as local or distant recurrences, for 428 patients (mean age, 46.9 years) who underwent 657 TSSMs and immediate breast reconstruction at the UCSF Medical Center in 2001-2010.

"The mastectomy incisions included radial, lateral, periareolar, and inframammary incisions, and the areolar and nipple complex tissue was separated from the dermal layer of skin by sharp dissection with inversion of the nipple skin to ensure the removal of all of the nipple duct tissue," Dr. Warren Peled said during a poster discussion. Of the 657 mastectomies, 412 were therapeutic procedures, and 245 (58 bilateral and 187 contralateral) were prophylactic, she said.

Most of the tumors were stage 0 (111) or stage I (135), although stage II (95), III (48), and IV (7) tumors were also observed, Dr. Warren Peled reported. Some 14 mastectomies were for recurrent cancer, she noted. In addition, 210 patients underwent neoadjuvant chemotherapy, 144 had postmastectomy radiation therapy, and 78 had adjuvant chemotherapy, she said.

With respect to nipple involvement on pathological analysis, 11 specimens had evidence of in situ cancer and 9 had evidence of invasive cancer, leading to re-excision in 7 cases, removal of the nipple-areolar complex (NAC) in 9 cases, and NAC radiation in 4 cases, said Dr. Warren Peled.

The conventional, two-stage, expander-implant method – in which a tissue expander placed under the chest muscle is implanted and gradually inflated to expand the tissue in preparation for the synthetic implant 3-6 months later – was used in 80% of the postmastectomy reconstructions, Dr. Warren Peled said. The remaining 20% of the reconstructions included either the placement of a permanent silicon implant at the time of mastectomy (4.7%) or autologous reconstruction (15.3%), she said.

A review of the oncologic outcomes in the 412 patients who underwent therapeutic mastectomies showed that, at a median follow-up of 28 months, four patients (1%) experienced local recurrence only, eight (1.9%) experienced distant recurrence only, and four experienced both local and distant recurrence (1%), Dr. Warren Peled reported. Among the local recurrences, two each were invasive (0.7%) and in situ cancer (1.8%), and among the distant recurrences, all eight (2.7) were invasive cancers. Among those with both local and distant recurrences, three (1%) and one (0.9%) were invasive and in situ, respectively, she said,

Of the 126 patients who had a minimum 36 months’ follow-up (median, 45 months), 2 patients (1.6%) had local recurrence only, one of which was invasive; 1 patient (0.8%) had distant recurrence only; and 1 (0.8%) had both, Dr. Peled said, noting that the recurrences in the latter two patients were invasive.

An assessment of ischemic complications showed 13 cases (1.9%) of partial nipple loss; 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis, Dr. Peled said, noting that the group’s current nipple loss rate is lower than 1%, thanks to serial improvements in surgical technique.

The findings indicate that TSSM "can be performed with low rates of nipple involvement and locoregional recurrence," Dr. Warren Peled stated. Although the short-term findings are encouraging, the study cannot speak to the long-term oncologic safety of the procedure. "Longer term follow-up is needed to confirm the oncologic safety over time," she said.

Dr. Warren Peled had no relevant financial conflicts to disclose.

SAN ANTONIO – Total skin-sparing mastectomy with complete preservation of the breast skin envelope was associated with favorable oncologic and ischemic outcomes in a large, high-risk cohort of women who underwent the procedure over a 10-year period in San Francisco, a study has shown.

The findings suggest that the surgery, which produces superior cosmesis and is associated with a high rate of patient satisfaction, is a reasonable option for many women facing therapeutic or prophylactic mastectomy, Dr. Anne G. Warren Peled said at the San Antonio Breast Cancer Symposium.

The total skin-sparing mastectomy (TSSM) allows preservation of the nipple-areola dermal layer when ductal tissue is removed during mastectomy. "The procedure is increasingly offered to women for both therapeutic and prophylactic indications, and when combined with immediate breast reconstruction, can produce excellent aesthetic results," explained Dr. Warren Peled, a surgical resident at the University of California, San Francisco.

Because the oncologic safety of the procedure and the potential for higher rates of postoperative complications continue to be debated, Dr. Warren Peled and her colleagues sought to evaluate both outcomes using data collected in a prospectively maintained database. The investigators analyzed patient and tumor characteristics, treatment details, and the development of any postoperative complications, as well as local or distant recurrences, for 428 patients (mean age, 46.9 years) who underwent 657 TSSMs and immediate breast reconstruction at the UCSF Medical Center in 2001-2010.

"The mastectomy incisions included radial, lateral, periareolar, and inframammary incisions, and the areolar and nipple complex tissue was separated from the dermal layer of skin by sharp dissection with inversion of the nipple skin to ensure the removal of all of the nipple duct tissue," Dr. Warren Peled said during a poster discussion. Of the 657 mastectomies, 412 were therapeutic procedures, and 245 (58 bilateral and 187 contralateral) were prophylactic, she said.

Most of the tumors were stage 0 (111) or stage I (135), although stage II (95), III (48), and IV (7) tumors were also observed, Dr. Warren Peled reported. Some 14 mastectomies were for recurrent cancer, she noted. In addition, 210 patients underwent neoadjuvant chemotherapy, 144 had postmastectomy radiation therapy, and 78 had adjuvant chemotherapy, she said.

With respect to nipple involvement on pathological analysis, 11 specimens had evidence of in situ cancer and 9 had evidence of invasive cancer, leading to re-excision in 7 cases, removal of the nipple-areolar complex (NAC) in 9 cases, and NAC radiation in 4 cases, said Dr. Warren Peled.

The conventional, two-stage, expander-implant method – in which a tissue expander placed under the chest muscle is implanted and gradually inflated to expand the tissue in preparation for the synthetic implant 3-6 months later – was used in 80% of the postmastectomy reconstructions, Dr. Warren Peled said. The remaining 20% of the reconstructions included either the placement of a permanent silicon implant at the time of mastectomy (4.7%) or autologous reconstruction (15.3%), she said.

A review of the oncologic outcomes in the 412 patients who underwent therapeutic mastectomies showed that, at a median follow-up of 28 months, four patients (1%) experienced local recurrence only, eight (1.9%) experienced distant recurrence only, and four experienced both local and distant recurrence (1%), Dr. Warren Peled reported. Among the local recurrences, two each were invasive (0.7%) and in situ cancer (1.8%), and among the distant recurrences, all eight (2.7) were invasive cancers. Among those with both local and distant recurrences, three (1%) and one (0.9%) were invasive and in situ, respectively, she said,

Of the 126 patients who had a minimum 36 months’ follow-up (median, 45 months), 2 patients (1.6%) had local recurrence only, one of which was invasive; 1 patient (0.8%) had distant recurrence only; and 1 (0.8%) had both, Dr. Peled said, noting that the recurrences in the latter two patients were invasive.

An assessment of ischemic complications showed 13 cases (1.9%) of partial nipple loss; 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis, Dr. Peled said, noting that the group’s current nipple loss rate is lower than 1%, thanks to serial improvements in surgical technique.

The findings indicate that TSSM "can be performed with low rates of nipple involvement and locoregional recurrence," Dr. Warren Peled stated. Although the short-term findings are encouraging, the study cannot speak to the long-term oncologic safety of the procedure. "Longer term follow-up is needed to confirm the oncologic safety over time," she said.

Dr. Warren Peled had no relevant financial conflicts to disclose.

SAN ANTONIO – Total skin-sparing mastectomy with complete preservation of the breast skin envelope was associated with favorable oncologic and ischemic outcomes in a large, high-risk cohort of women who underwent the procedure over a 10-year period in San Francisco, a study has shown.

The findings suggest that the surgery, which produces superior cosmesis and is associated with a high rate of patient satisfaction, is a reasonable option for many women facing therapeutic or prophylactic mastectomy, Dr. Anne G. Warren Peled said at the San Antonio Breast Cancer Symposium.

The total skin-sparing mastectomy (TSSM) allows preservation of the nipple-areola dermal layer when ductal tissue is removed during mastectomy. "The procedure is increasingly offered to women for both therapeutic and prophylactic indications, and when combined with immediate breast reconstruction, can produce excellent aesthetic results," explained Dr. Warren Peled, a surgical resident at the University of California, San Francisco.

Because the oncologic safety of the procedure and the potential for higher rates of postoperative complications continue to be debated, Dr. Warren Peled and her colleagues sought to evaluate both outcomes using data collected in a prospectively maintained database. The investigators analyzed patient and tumor characteristics, treatment details, and the development of any postoperative complications, as well as local or distant recurrences, for 428 patients (mean age, 46.9 years) who underwent 657 TSSMs and immediate breast reconstruction at the UCSF Medical Center in 2001-2010.

"The mastectomy incisions included radial, lateral, periareolar, and inframammary incisions, and the areolar and nipple complex tissue was separated from the dermal layer of skin by sharp dissection with inversion of the nipple skin to ensure the removal of all of the nipple duct tissue," Dr. Warren Peled said during a poster discussion. Of the 657 mastectomies, 412 were therapeutic procedures, and 245 (58 bilateral and 187 contralateral) were prophylactic, she said.

Most of the tumors were stage 0 (111) or stage I (135), although stage II (95), III (48), and IV (7) tumors were also observed, Dr. Warren Peled reported. Some 14 mastectomies were for recurrent cancer, she noted. In addition, 210 patients underwent neoadjuvant chemotherapy, 144 had postmastectomy radiation therapy, and 78 had adjuvant chemotherapy, she said.

With respect to nipple involvement on pathological analysis, 11 specimens had evidence of in situ cancer and 9 had evidence of invasive cancer, leading to re-excision in 7 cases, removal of the nipple-areolar complex (NAC) in 9 cases, and NAC radiation in 4 cases, said Dr. Warren Peled.

The conventional, two-stage, expander-implant method – in which a tissue expander placed under the chest muscle is implanted and gradually inflated to expand the tissue in preparation for the synthetic implant 3-6 months later – was used in 80% of the postmastectomy reconstructions, Dr. Warren Peled said. The remaining 20% of the reconstructions included either the placement of a permanent silicon implant at the time of mastectomy (4.7%) or autologous reconstruction (15.3%), she said.

A review of the oncologic outcomes in the 412 patients who underwent therapeutic mastectomies showed that, at a median follow-up of 28 months, four patients (1%) experienced local recurrence only, eight (1.9%) experienced distant recurrence only, and four experienced both local and distant recurrence (1%), Dr. Warren Peled reported. Among the local recurrences, two each were invasive (0.7%) and in situ cancer (1.8%), and among the distant recurrences, all eight (2.7) were invasive cancers. Among those with both local and distant recurrences, three (1%) and one (0.9%) were invasive and in situ, respectively, she said,

Of the 126 patients who had a minimum 36 months’ follow-up (median, 45 months), 2 patients (1.6%) had local recurrence only, one of which was invasive; 1 patient (0.8%) had distant recurrence only; and 1 (0.8%) had both, Dr. Peled said, noting that the recurrences in the latter two patients were invasive.

An assessment of ischemic complications showed 13 cases (1.9%) of partial nipple loss; 10 cases (1.5%) of complete nipple loss, and 78 cases (11.8%) of skin flap necrosis, Dr. Peled said, noting that the group’s current nipple loss rate is lower than 1%, thanks to serial improvements in surgical technique.

The findings indicate that TSSM "can be performed with low rates of nipple involvement and locoregional recurrence," Dr. Warren Peled stated. Although the short-term findings are encouraging, the study cannot speak to the long-term oncologic safety of the procedure. "Longer term follow-up is needed to confirm the oncologic safety over time," she said.

Dr. Warren Peled had no relevant financial conflicts to disclose.

SAN ANTONIO – Long-term upper-extremity pain and functional impairment following breast cancer surgery are reduced by an innovative physical therapy–centered surveillance program, according to a 5-year prospective study.

The program was developed at the breast care center of Walter Reed National Military Medical Center, Bethesda, Md. It begins with a preoperative patient interview and structured evaluation by a physical therapist. The assessment includes what physical therapists call an upper-quarter screen, which evaluates shoulder range of motion, strength, and arm volume. Self-reported pain, fatigue, function, and activity level are recorded.

At that time, the patient is also instructed in a home exercise program she is to start 2 weeks post surgery. These are simple range-of-motion exercises focused on forward flexion overhead; abduction; internal and external rotation of the glenohumeral joint; and scapular retraction, Nicole L. Stout explained at the San Antonio Breast Cancer Symposium.

The patient is subsequently seen by the physical therapist (in conjunction with her regular follow-up visits with an oncologist or surgeon) at 1, 3, 6, 9, 12, and 60 months post surgery. If upper-extremity dysfunction worsens, more intensive interventions are introduced.

The rationale for this prospective surveillance program lies in an understanding that the shoulder and arm impairments caused by breast cancer surgery and radiation therapy are typically subtle initially, but if left unidentified and uncorrected, they often progress to serious rotator cuff damage, "frozen" shoulder, and debilitating lymphedema, according to Ms. Stout, a civilian research physical therapist at the military center.

She had previously presented her 1-year prospective outcomes. This time around, she presented prospective 5-year follow-up data on 86 breast cancer patients who participated in the program. This is the first prospective cohort study in the United States to track breast cancer–related upper-extremity morbidity and functional outcomes for this long a time period.

The 12-month and 5-year visits included formal assessment of upper-extremity outcomes using the Harvard Alumni Activity Survey, the Upper Limb Disability Questionnaire, and the Short Form-36.

At 5 years, 11% of the women had stage I/II lymphedema and 38% had subclinical lymphedema (defined as less than 3% arm volume swelling as measured by a Perometer). These results compare favorably with those of published studies on lymphedema, which have reported long-term rates of stage I-III arm swelling in the 40%-60% range, she noted.

In all, 18% of patients reported arm numbness at 5 years, 17% noted shoulder pain, 3% had neck pain, and 1% had chest wall pain.

One-third of subjects reported fatigue of level 3 or more on a 10-point visual analog scale. Again, other investigators have documented long-term rates of clinically significant fatigue in the 50%-60% range.

At 5 years post surgery, patients demonstrated less impairment of physical activity than at preoperative baseline. At baseline, 33% had significant limitations in terms of carrying heavy objects, performing household chores, and other physical activities. After 5 years of prospective surveillance and tailored physical therapy, only 20% of patients had physical activity limitations.

However, 68% of patients reported experiencing some restrictions on their social activity at 5 years, and 52% experienced limitations on their recreational activities.

The study was funded by the medical center. Ms. Stout declared having no financial conflicts of interest.

SAN ANTONIO – Long-term upper-extremity pain and functional impairment following breast cancer surgery are reduced by an innovative physical therapy–centered surveillance program, according to a 5-year prospective study.

The program was developed at the breast care center of Walter Reed National Military Medical Center, Bethesda, Md. It begins with a preoperative patient interview and structured evaluation by a physical therapist. The assessment includes what physical therapists call an upper-quarter screen, which evaluates shoulder range of motion, strength, and arm volume. Self-reported pain, fatigue, function, and activity level are recorded.

At that time, the patient is also instructed in a home exercise program she is to start 2 weeks post surgery. These are simple range-of-motion exercises focused on forward flexion overhead; abduction; internal and external rotation of the glenohumeral joint; and scapular retraction, Nicole L. Stout explained at the San Antonio Breast Cancer Symposium.

The patient is subsequently seen by the physical therapist (in conjunction with her regular follow-up visits with an oncologist or surgeon) at 1, 3, 6, 9, 12, and 60 months post surgery. If upper-extremity dysfunction worsens, more intensive interventions are introduced.

The rationale for this prospective surveillance program lies in an understanding that the shoulder and arm impairments caused by breast cancer surgery and radiation therapy are typically subtle initially, but if left unidentified and uncorrected, they often progress to serious rotator cuff damage, "frozen" shoulder, and debilitating lymphedema, according to Ms. Stout, a civilian research physical therapist at the military center.

She had previously presented her 1-year prospective outcomes. This time around, she presented prospective 5-year follow-up data on 86 breast cancer patients who participated in the program. This is the first prospective cohort study in the United States to track breast cancer–related upper-extremity morbidity and functional outcomes for this long a time period.

The 12-month and 5-year visits included formal assessment of upper-extremity outcomes using the Harvard Alumni Activity Survey, the Upper Limb Disability Questionnaire, and the Short Form-36.

At 5 years, 11% of the women had stage I/II lymphedema and 38% had subclinical lymphedema (defined as less than 3% arm volume swelling as measured by a Perometer). These results compare favorably with those of published studies on lymphedema, which have reported long-term rates of stage I-III arm swelling in the 40%-60% range, she noted.

In all, 18% of patients reported arm numbness at 5 years, 17% noted shoulder pain, 3% had neck pain, and 1% had chest wall pain.

One-third of subjects reported fatigue of level 3 or more on a 10-point visual analog scale. Again, other investigators have documented long-term rates of clinically significant fatigue in the 50%-60% range.

At 5 years post surgery, patients demonstrated less impairment of physical activity than at preoperative baseline. At baseline, 33% had significant limitations in terms of carrying heavy objects, performing household chores, and other physical activities. After 5 years of prospective surveillance and tailored physical therapy, only 20% of patients had physical activity limitations.

However, 68% of patients reported experiencing some restrictions on their social activity at 5 years, and 52% experienced limitations on their recreational activities.

The study was funded by the medical center. Ms. Stout declared having no financial conflicts of interest.

SAN ANTONIO – Long-term upper-extremity pain and functional impairment following breast cancer surgery are reduced by an innovative physical therapy–centered surveillance program, according to a 5-year prospective study.

The program was developed at the breast care center of Walter Reed National Military Medical Center, Bethesda, Md. It begins with a preoperative patient interview and structured evaluation by a physical therapist. The assessment includes what physical therapists call an upper-quarter screen, which evaluates shoulder range of motion, strength, and arm volume. Self-reported pain, fatigue, function, and activity level are recorded.

At that time, the patient is also instructed in a home exercise program she is to start 2 weeks post surgery. These are simple range-of-motion exercises focused on forward flexion overhead; abduction; internal and external rotation of the glenohumeral joint; and scapular retraction, Nicole L. Stout explained at the San Antonio Breast Cancer Symposium.

The patient is subsequently seen by the physical therapist (in conjunction with her regular follow-up visits with an oncologist or surgeon) at 1, 3, 6, 9, 12, and 60 months post surgery. If upper-extremity dysfunction worsens, more intensive interventions are introduced.

The rationale for this prospective surveillance program lies in an understanding that the shoulder and arm impairments caused by breast cancer surgery and radiation therapy are typically subtle initially, but if left unidentified and uncorrected, they often progress to serious rotator cuff damage, "frozen" shoulder, and debilitating lymphedema, according to Ms. Stout, a civilian research physical therapist at the military center.

She had previously presented her 1-year prospective outcomes. This time around, she presented prospective 5-year follow-up data on 86 breast cancer patients who participated in the program. This is the first prospective cohort study in the United States to track breast cancer–related upper-extremity morbidity and functional outcomes for this long a time period.

The 12-month and 5-year visits included formal assessment of upper-extremity outcomes using the Harvard Alumni Activity Survey, the Upper Limb Disability Questionnaire, and the Short Form-36.

At 5 years, 11% of the women had stage I/II lymphedema and 38% had subclinical lymphedema (defined as less than 3% arm volume swelling as measured by a Perometer). These results compare favorably with those of published studies on lymphedema, which have reported long-term rates of stage I-III arm swelling in the 40%-60% range, she noted.

In all, 18% of patients reported arm numbness at 5 years, 17% noted shoulder pain, 3% had neck pain, and 1% had chest wall pain.

One-third of subjects reported fatigue of level 3 or more on a 10-point visual analog scale. Again, other investigators have documented long-term rates of clinically significant fatigue in the 50%-60% range.

At 5 years post surgery, patients demonstrated less impairment of physical activity than at preoperative baseline. At baseline, 33% had significant limitations in terms of carrying heavy objects, performing household chores, and other physical activities. After 5 years of prospective surveillance and tailored physical therapy, only 20% of patients had physical activity limitations.

However, 68% of patients reported experiencing some restrictions on their social activity at 5 years, and 52% experienced limitations on their recreational activities.

The study was funded by the medical center. Ms. Stout declared having no financial conflicts of interest.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Adjuvant therapy with ibandronate made no impact on disease-free survival or overall survival rates in women with node-positive, early breast cancer that had been treated with dose-dense chemotherapy in a phase-III study of more than 3,000 patients.

The 3-year disease-free survival rate of 87.6% in those on ibandronate (Boniva) was a close match with the 87.2% that was recorded in a control group under observation. The 3-year overall survival rates also were similar, at 94.7% with ibandronate and 94.1% with observation.

There were no differences in disease-free survival for any of the subgroup analyses, Volker Möbus, Ph.D., reported at the annual San Antonio Breast Cancer Symposium.

"The interim analysis for efficacy showed little difference between treatment arms with and without ibandronate," said Dr. Möbus, head of obstetrics and gynecology at Klinikum Frankfurt (Germany) Höchst. The interim analysis was planned when 50% (405) of the expected events had been reached.

The GAIN (German Adjuvant Intergroup Node-Positive Study) trial is a controlled, nonblinded, randomized, phase III trial. The investigators compared epirubicin, cyclophosphamide, and paclitaxel chemotherapy with epirubicin and cyclophosphamide followed by paclitaxel and capecitabine. In addition, patients were further randomized in a 2:1 ratio to receive ibandronate (50 mg/day for 2 years) or observation alone.

Dr. Möbus presented the results for the ibandronate component of the trial. The chemotherapy results have not been released.

The GAIN trial randomized 3,023 women between June 2004 and August 2008. The protocol required that they be aged from 18 to younger than 65 years, and have histologically confirmed, lymph node–positive uni- or bilateral primary breast cancer, as well as an ECOG performance score of at least 2. Patients could have no distant metastases, and a life expectancy of at least 10 years was required. The median age was 50 years, and median follow-up was 39 months.

In all, 2,015 and 1,008 patients, respectively, were randomized to ibandronate vs. observation. However, 15 patients in the observation arm also started ibandronate, for a total of 1,870 patients. Some 18% of patients on ibandronate discontinued use of the drug for a variety of reasons, including death, adverse events, and loss to follow-up, noted Dr. Möbus.

An oral bisphosphonate, ibandronate is approved for the prevention and treatment of osteoporosis in postmenopausal women in the United States.

Financial support for the study was provided by Amgen and Roche. Dr. Möbus and several of his coinvestigators disclosed financial relationships with Amgen and Roche.

SAN ANTONIO – Curbing colony-stimulating factor use at the start of dose-dense chemotherapy in Medicare patients with hormone receptor–positive breast cancer would save nearly $40 million per year in a population unlikely to gain meaningful benefit from such therapy, according to a new study.

The use of first-cycle colony-stimulating factor (CSF) therapy took off in 2002, Dr. Dawn L. Hershman told attendees at the San Antonio Breast Cancer Symposium. That was the year the benefits of dose-dense chemotherapy were reported, and pegfilgrastim (Neulasta), a granulocyte CSF that was easier to use than those previously available, received marketing approval from the Food and Drug Administration.

A new analysis of Medicare data shows that first-cycle use of CSFs in patients with stage I-III breast cancer jumped from 13% during 1998-2002 to 68% in 2002-2005, reported Dr. Hershman of Columbia University, New York.

In the last half-decade, however, multiple major studies have convincingly shown that the benefits of dose-dense chemotherapy with first-cycle CSFs are confined to breast cancer patients with hormone receptor–negative tumors, according to Dr. Hershman.

For example, one meta-analysis of studies comparing dose-dense to standard chemotherapy in 3,337 estrogen receptor–negative patients showed that dose-dense chemotherapy yielded a 29% reduction in recurrence risk and a 16% improvement in overall survival. In 1,344 estrogen receptor–positive patients, in contrast, dose-dense chemotherapy provided a nonsignificant 8% reduction in recurrence risk and no hint of a benefit in terms of overall survival (J. Natl. Cancer Inst. 2010;102:1845-54).

For the new study, Dr. Hershman and her coauthors identified 10,773 patients in a combined Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were over age 65 with stage I-III breast cancer diagnosed during 1998-2005, and who had at least one chemotherapy claim within 6 months of diagnosis. Of these, 5,266 had a CSF claim during therapy. First-cycle CSF use increased from 13% to 68% over the study period, and the use of pegfilgrastim jumped from 4% to 84%.

"We’re very quick in oncology to adopt, and we never pull back – even when there’s evidence against," Dr. Hershman said. "If we have to make decisions in terms of controlling costs, we shouldn’t be giving drugs that are costly and have no benefit."

Dr. Thomas J. Smith, chair of the session at which Dr. Hershman presented the new study, took the argument further, citing Dr. Hershman’s own earlier study suggesting that CSF therapy in elderly women may actually cause significant harm. In an analysis in which she merged Medicare and SEER databases, Dr. Hershman had reported a twofold increased risk of acute myeloid leukemia and myelodysplastic syndrome in elderly women who received a CSF compared with those who did not (J. Natl. Cancer Inst. 2007;99:196-205).

"All that nearly $40 million per year in Medicare expenditures for colony-stimulating factors is buying is toxicity. You’re not buying any disease benefit," argued Dr. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

He proposed that it’s time to consider putting the use of CSFs and dose-dense chemotherapy in elderly patients with hormone receptor–positive tumors on the Quality Oncology Practice Initiative's "do not use" list.

"My thought would be at a minimum we should explain the very small, at-most 8% relative benefit, and the risks. And most people, I think, given the numbers, would say, ‘I’ll take regular chemotherapy, thank you,’ " Dr. Smith predicted.

Dr. Hershman declared having no financial conflicts.

SAN ANTONIO – Curbing colony-stimulating factor use at the start of dose-dense chemotherapy in Medicare patients with hormone receptor–positive breast cancer would save nearly $40 million per year in a population unlikely to gain meaningful benefit from such therapy, according to a new study.

The use of first-cycle colony-stimulating factor (CSF) therapy took off in 2002, Dr. Dawn L. Hershman told attendees at the San Antonio Breast Cancer Symposium. That was the year the benefits of dose-dense chemotherapy were reported, and pegfilgrastim (Neulasta), a granulocyte CSF that was easier to use than those previously available, received marketing approval from the Food and Drug Administration.

A new analysis of Medicare data shows that first-cycle use of CSFs in patients with stage I-III breast cancer jumped from 13% during 1998-2002 to 68% in 2002-2005, reported Dr. Hershman of Columbia University, New York.

In the last half-decade, however, multiple major studies have convincingly shown that the benefits of dose-dense chemotherapy with first-cycle CSFs are confined to breast cancer patients with hormone receptor–negative tumors, according to Dr. Hershman.

For example, one meta-analysis of studies comparing dose-dense to standard chemotherapy in 3,337 estrogen receptor–negative patients showed that dose-dense chemotherapy yielded a 29% reduction in recurrence risk and a 16% improvement in overall survival. In 1,344 estrogen receptor–positive patients, in contrast, dose-dense chemotherapy provided a nonsignificant 8% reduction in recurrence risk and no hint of a benefit in terms of overall survival (J. Natl. Cancer Inst. 2010;102:1845-54).

For the new study, Dr. Hershman and her coauthors identified 10,773 patients in a combined Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were over age 65 with stage I-III breast cancer diagnosed during 1998-2005, and who had at least one chemotherapy claim within 6 months of diagnosis. Of these, 5,266 had a CSF claim during therapy. First-cycle CSF use increased from 13% to 68% over the study period, and the use of pegfilgrastim jumped from 4% to 84%.

"We’re very quick in oncology to adopt, and we never pull back – even when there’s evidence against," Dr. Hershman said. "If we have to make decisions in terms of controlling costs, we shouldn’t be giving drugs that are costly and have no benefit."

Dr. Thomas J. Smith, chair of the session at which Dr. Hershman presented the new study, took the argument further, citing Dr. Hershman’s own earlier study suggesting that CSF therapy in elderly women may actually cause significant harm. In an analysis in which she merged Medicare and SEER databases, Dr. Hershman had reported a twofold increased risk of acute myeloid leukemia and myelodysplastic syndrome in elderly women who received a CSF compared with those who did not (J. Natl. Cancer Inst. 2007;99:196-205).

"All that nearly $40 million per year in Medicare expenditures for colony-stimulating factors is buying is toxicity. You’re not buying any disease benefit," argued Dr. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

He proposed that it’s time to consider putting the use of CSFs and dose-dense chemotherapy in elderly patients with hormone receptor–positive tumors on the Quality Oncology Practice Initiative's "do not use" list.

"My thought would be at a minimum we should explain the very small, at-most 8% relative benefit, and the risks. And most people, I think, given the numbers, would say, ‘I’ll take regular chemotherapy, thank you,’ " Dr. Smith predicted.

Dr. Hershman declared having no financial conflicts.

SAN ANTONIO – Curbing colony-stimulating factor use at the start of dose-dense chemotherapy in Medicare patients with hormone receptor–positive breast cancer would save nearly $40 million per year in a population unlikely to gain meaningful benefit from such therapy, according to a new study.

The use of first-cycle colony-stimulating factor (CSF) therapy took off in 2002, Dr. Dawn L. Hershman told attendees at the San Antonio Breast Cancer Symposium. That was the year the benefits of dose-dense chemotherapy were reported, and pegfilgrastim (Neulasta), a granulocyte CSF that was easier to use than those previously available, received marketing approval from the Food and Drug Administration.

A new analysis of Medicare data shows that first-cycle use of CSFs in patients with stage I-III breast cancer jumped from 13% during 1998-2002 to 68% in 2002-2005, reported Dr. Hershman of Columbia University, New York.

In the last half-decade, however, multiple major studies have convincingly shown that the benefits of dose-dense chemotherapy with first-cycle CSFs are confined to breast cancer patients with hormone receptor–negative tumors, according to Dr. Hershman.

For example, one meta-analysis of studies comparing dose-dense to standard chemotherapy in 3,337 estrogen receptor–negative patients showed that dose-dense chemotherapy yielded a 29% reduction in recurrence risk and a 16% improvement in overall survival. In 1,344 estrogen receptor–positive patients, in contrast, dose-dense chemotherapy provided a nonsignificant 8% reduction in recurrence risk and no hint of a benefit in terms of overall survival (J. Natl. Cancer Inst. 2010;102:1845-54).

For the new study, Dr. Hershman and her coauthors identified 10,773 patients in a combined Surveillance, Epidemiology, and End Results (SEER)-Medicare database who were over age 65 with stage I-III breast cancer diagnosed during 1998-2005, and who had at least one chemotherapy claim within 6 months of diagnosis. Of these, 5,266 had a CSF claim during therapy. First-cycle CSF use increased from 13% to 68% over the study period, and the use of pegfilgrastim jumped from 4% to 84%.

"We’re very quick in oncology to adopt, and we never pull back – even when there’s evidence against," Dr. Hershman said. "If we have to make decisions in terms of controlling costs, we shouldn’t be giving drugs that are costly and have no benefit."

Dr. Thomas J. Smith, chair of the session at which Dr. Hershman presented the new study, took the argument further, citing Dr. Hershman’s own earlier study suggesting that CSF therapy in elderly women may actually cause significant harm. In an analysis in which she merged Medicare and SEER databases, Dr. Hershman had reported a twofold increased risk of acute myeloid leukemia and myelodysplastic syndrome in elderly women who received a CSF compared with those who did not (J. Natl. Cancer Inst. 2007;99:196-205).

"All that nearly $40 million per year in Medicare expenditures for colony-stimulating factors is buying is toxicity. You’re not buying any disease benefit," argued Dr. Smith, director of palliative care and Harry J. Duffey Family Professor of Palliative Care at Johns Hopkins University, Baltimore.

He proposed that it’s time to consider putting the use of CSFs and dose-dense chemotherapy in elderly patients with hormone receptor–positive tumors on the Quality Oncology Practice Initiative's "do not use" list.

"My thought would be at a minimum we should explain the very small, at-most 8% relative benefit, and the risks. And most people, I think, given the numbers, would say, ‘I’ll take regular chemotherapy, thank you,’ " Dr. Smith predicted.

Dr. Hershman declared having no financial conflicts.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – The combination of topical 5% imiquimod plus systemic nanoparticle albumin-bound paclitaxel showed excellent clinical efficacy and was well tolerated for the treatment of cutaneous metastases of breast cancer in a phase II study.

Among the 11 patients who were able to complete the novel combined chemoimmunotherapy regimen, 5 had a complete response, meaning 100% clearance of treated skin lesions at week 24.

In addition, one patient had a partial response, defined as a greater than 50% reduction in the size of the largest treated lesion. Four patients had stable disease, with less than 50% reductions in lesion size. One patient experienced progressive disease, with a 25% increase in target lesion size, Dr. Lupe G. Salazar reported at the San Antonio Breast Cancer Symposium.

Fifteen heavily pretreated breast cancer patients were enrolled in the single-arm, nonrandomized study. All had skin metastases no longer amenable to standard therapies.

The chemoimmunotherapy regimen consisted of three treatment cycles. Each 4-week cycle consisted of application of topical 5% imiquimod to target cutaneous lesions on 4 days per week plus systemic albumin-bound paclitaxel (Abraxane) at 100 mg/m² on days 1, 8, 15, and 28, explained Dr. Salazar of the University of Washington, Seattle.

Treatment-related toxicities included neutropenia, lymphopenia, anemia, nausea, and fatigue; 34% of toxicities were grade 1, 56% were grade 2, and the remaining 10% were grade 3.

Four of 15 subjects were unable to complete the treatment regimen, having withdrawn due to progression of visceral disease.

The rationale for the imiquimod plus nanoparticle albumin-bound (nab) paclitaxel (Abraxane) therapy derives from previous evidence that imiquimod, a toll-like receptor-7 agonist, has shown clinical efficacy against cutaneous metastases. Imiquimod stimulates secretion of Th1 cytokines and upregulates immune costimulatory molecules at the tumor site. Tumor-specific T cell immunity and tumor growth inhibition are enhanced. Moreover, paclitaxel has been shown to increase serum interferon-gamma levels and boost natural killer cell activity. Thus, the working hypothesis was that nab-paclitaxel would augment imiquimod’s antitumor effects, according to Dr. Salazar.

She and her coinvestigators examined the combination therapy’s impact upon endogenous tumor-specific immunity. They obtained pre- and posttreatment 2-mm skin biopsies from target lesions and were able to demonstrate that the treatment marginally enhanced endogenous immunity to the well-known breast cancer antigens HER2, p53, melanoma-associated antigen 3 (MAGE-3), insulin growth factor binding protein-2 (IGFBP-2), and topoisomerase IIa (TOPO-IIa).

The study was funded by a grant from the National Cancer Institute. Dr. Salazar declared having no relevant financial interests.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Combination therapy with anastrozole and fulvestrant might be a new first-line treatment option for postmenopausal women with hormone receptor–positive breast cancer.

Phase III trial results demonstrated a statistically significant progression-free survival benefit with the combination therapy, compared with anastrozole monotherapy, Dr. Rita S. Mehta reported at the San Antonio Breast Cancer Symposium. Tamoxifen-naive patients, in particular, appear to reap the most benefit.

Among the 694 patients analyzed in the Southwest Oncology Group (SWOG)-S0226 trial of anastrozole (Arimidex) vs. anastrozole plus fulvestrant (Faslodex), the median progression-free and overall survival rates of the 349 women randomized to combination therapy were longer by 1.5 months and more than 6 months, respectively, than in 345 women randomized to monotherapy, according to Dr. Mehta of the University of California, Irvine.

The combination therapy "is the first new treatment in more than a decade that gives women with hormone receptor–positive metastatic breast cancer an overall survival benefit," she said.

Further, in a subset analysis, tamoxifen-naive patients randomized to combination therapy survived more than 4 months longer without disease progression than those in the monotherapy group, Dr. Mehta said, noting that, among tamoxifen-pretreated women, the progression-free survival benefit was nearly the same as that observed in the overall study population.

All of the study patients, median age 65 years, were postmenopausal with estrogen or progesterone receptor–positive metastatic breast cancer, and none had been previously treated for metastatic disease, Dr. Mehta explained.

Women with a history of previous adjuvant aromatase inhibitor therapy or neoadjuvant or adjuvant chemotherapy were eligible for inclusion only if their prior treatment was completed more than 12 months prior, she said. Previous tamoxifen treatment was also allowed, but approximately 60% of the study population was tamoxifen-naive.

From 2004-2009, eligible patients were randomized to receive 1 mg of anastrozole daily, either alone or in combination with an intramuscular injection of fulvestrant, dosed as follows: 500 mg on the first day; 200 mg on days 14 and 28; and 250 mg monthly thereafter. The primary study end point was progression-free survival, Dr. Mehta said. Upon disease progression, patients randomized to monotherapy were encouraged to crossover to combination therapy, "unless they were candidates for immediate chemotherapy," she explained.

During the period of analysis, 287 of the monotherapy patients and 261 of the combination therapy patients experienced disease progression after a median 13.5 months and 15.0 months, respectively. Median overall survival was 41.3 months in the monotherapy group and 47.7 months in the combination group, reported Dr. Mehta.

Randomization was stratified by adjuvant tamoxifen to assess a possible differential benefit of fulvestrant in the two strata, Dr. Mehta said. In a subset analysis of the 414 tamoxifen-naive patients, median progression-free survival was 12.6 months for monotherapy and 17.0 months for combination therapy; median overall survival was 39.7 months and 47.7 months, respectively, she said.

Among the patients pretreated with tamoxifen, median progression-free survival was 14.1 months with monotherapy and 13.5 months with combination therapy; median overall survival was 44.5 months and 49.6 months, respectively. The observed survival benefit was independent of age, HER2 status, sites of metastasis, time since primary diagnosis, disease measurability, and adjuvant chemotherapy, Dr. Mehta stated.

Although it is possible that prior tamoxifen treatment may predict outcomes, "it’s too soon to say," according to Dr. Mehta. The findings require prospective validation, she noted: "We need to better understand other possible factors, because the prior tamoxifen factor could be a false lead from an unplanned analysis."

Treatment-related adverse events in the combination group included three deaths – two attributed to pulmonary embolism and one to cerebrovascular ischemia; one grade 4 pulmonary embolism; and one grade 4 neutropenia and lymphopenia, Dr. Mehta stated. Four patients in the monotherapy group experienced grade 4 toxicities, including thrombosis/embolism, arthralgia, thrombocytopenia, and dyspnea, she said.

Grade 3 toxicities, including musculoskeletal pain, fatigue, and gastrointestinal symptoms were reported in approximately 13% of the combination group and 11% of the monotherapy group, "but very few patients stopped treatment because of adverse events or side effects," she said.

The findings suggest that combination anastrozole and fulvestrant therapy amps up the anti-estrogen benefits of anastrozole alone in postmenopausal breast cancer when used as a first-line therapy, Dr. Mehta stressed.

This is in contrast, she noted, to previously reported first results from the randomized FACT study in which the combination therapy did not improve overall survival among postmenopausal women with hormone receptor–positive advanced breast cancer in first relapse.

"The next step for researchers will be to try the combination in even earlier stages of breast cancer to test whether long-term cures could be increased at those stages," Dr. Mehta concluded.

Dr. Mehta disclosed receiving grant and research support from AstraZeneca.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Physicians tend to broadly overestimate their own breast cancer patients’ compliance with adjuvant aromatase inhibitor therapy, according to a large observational German study.

Among 2,313 postmenopausal breast cancer patients who were enrolled in the ongoing COMPACT (Compliance and Arthralgias in Clinical Therapy) study, 80.5% stated that they took all or nearly all of their prescribed anastrozole tablets during their first year on adjuvant endocrine therapy.

In contrast, 93.2% of their oncologists indicated they believed those same patients had taken all or nearly all of their medication, Dr. Peyman Hadji reported at the San Antonio Breast Cancer Symposium.

Among COMPACT participants, 11.9% indicated that they experienced pre-existing arthralgias within 4 weeks prior to going on the aromatase inhibitor. Another 17% reported new-onset arthralgias after starting on anastrozole, according to Dr. Hadji of the University Hospital of Giessen and Marburg (Germany) GmbH.

Session chair Dr. Thomas J. Smith said that these initial data from the COMPACT study contain a key take-home message: "I think it certainly behooves me as a breast cancer doctor to ask every time, ‘Are you having trouble with these drugs?’ because people do have trouble with these drugs, and they don’t want to bother us."

Another take-home point is that although roughly 12% of breast cancer patients have pre-existing arthralgias, the prescription of an aromatase inhibitor increases the population of affected individuals by close to an absolute 20%, added Dr. Smith, director of palliative care and professor of oncology at Johns Hopkins University, Baltimore.

Dr. Hadji said that going forward, COMPACT will assess the frequency and severity of aromatase inhibitor–associated arthralgias in real-world clinical practice, will chart rates of arthralgia-related treatment noncompliance, and will document the effectiveness and costs of various treatments.

Dr. Smith observed that to date there is a noteworthy lack of good-quality, randomized trial data to guide treatment of aromatase inhibitor–associated arthralgias. Dr. Hadji concurred. He said he and his colleagues have had favorable experiences using NSAIDs, but that’s anecdotal experience. Regarding high-quality data, he cited what he termed a "wonderful" double-blind study showing benefit for acupuncture (J. Clin. Oncol. 2010;28:1154-60).

"The data were really fascinating, but we couldn’t find anybody in our clinic to start doing it. For whatever reasons, oncologists don’t like putting needles into patients," he quipped.

The COMPACT study is sponsored by AstraZeneca. Dr. Hadji serves as a consultant to the company.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.

SAN ANTONIO – Trastuzumab emtansine – the novel antibody-drug conjugate known as T-DM1 – provides significantly greater patient-reported quality of life and treatment tolerability than do standard trastuzumab and docetaxel in patients with previously untreated HER2-positive metastatic breast cancer, a phase II study indicates.

This is the same randomized, multicenter, open-label, phase II study that previously reported a highly significant 41% improvement in the efficacy end point of investigator-reported progression-free survival favoring trastuzumab emtansine by a margin of 14.2 months vs. 9.2 months, Dr. Giulia V. Bianchi noted at the annual San Antonio Breast Cancer Symposium.

Her new report presented key patient-reported outcomes, such as quality of life measurements. These data further define T-DM1 as a therapy that’s superior to what’s currently available, according to Dr. Bianchi of the Italian National Cancer Institute, Milan.

The primary patient-reported outcome was time to symptom progression (defined by at least a 5-point decrease from baseline on the Functional Assessment of Cancer Therapy–Breast Trial Outcome Index). Among 132 evaluable study participants, worsening of the FACT-B TOI score was significantly delayed in patients who were randomized to T-DM1; it occurred at a mean of 7.5 months in these patients, compared with 3.5 months in subjects assigned to trastuzumab (Herceptin) plus docetaxel (Taxotere).

The chief benefit of T-DM1 showed up on the physical well being subscale of the FACT-B TOI. Five of the seven items on the physical well-being subscale (lack of energy, feel ill, trouble meeting needs of family, bothered by side effects, and forced to spend time in bed) showed significantly better mean scores with T-DM1. The other two physical well-being items (nausea and pain) trended better in the T-DM1 group, but not significantly so.

The incidence of grade 3 or greater adverse events was 46% in the T-DM1 group vs. 89% in controls. Only 7% of patients in the T-DM1 arm stopped therapy because of adverse events, compared with 30% in the trastuzumab-plus-docetaxel arm.

Taken together, these data support the notion that T-DM1 is an advance in terms of tolerability, which in turn contributes to enhanced efficacy, safety, and health-related quality of life, Dr. Bianchi concluded.

The phase II study was sponsored by Genentech, which has big plans for T-DM1. The phase III MARIANNE trial, which is comparing T-DM1 as single-agent therapy with T-DM1 plus pertuzumab and with various trastuzumab/taxane combinations as first-line therapy in advanced HER2-positive breast cancer, is well underway. The phase III EMILIA trial is looking at T-DM1 for second-line use in advanced HER2-positive breast cancer. In addition, the monoclonal antibody and drug conjugate is under development for adjuvant and neoadjuvant use in early-stage breast cancer. T-DM1 is also being scrutinized as a potential treatment for HER2-positive gastric cancer.

Dr. Bianchi declared she has no financial conflicts of interest.