One small controlled trial has suggested there are improvements in overall survival after two courses of high-dose chemotherapy supported by autologous stem-cell transplantation, compared with standard-dose chemotherapy, the authors explain in the January 1st issue of the Journal of Clinical Oncology.

Dr. Michael Crump at Princess Margaret Hospital in Toronto and colleagues investigated whether the addition of one course of high-dose chemotherapy and autologous stem-cell transplantation could improve overall survival among women with metastatic breast cancer who responded to optimal chemotherapy. They also evaluated the effects of this treatment on quality of life.

Similar proportions of women in the two groups experienced complete and partial responses, the authors report.

Median overall survival was 24 months for patients receiving high-dose chemotherapy, compared with 28 months for patients receiving standard-dose chemotherapy.

Overall survival also did not differ among those who had complete responses or no evidence of disease after induction therapy, for those without visceral disease, or by type of induction therapy.

Median progression-free survival was significantly longer for women who had high-dose chemotherapy (11 months) than for those who had standard-dose chemotherapy (9 months), the researchers report.

Grade 3 and 4 toxicity was also significantly more common after high-dose chemotherapy, the investigators note.

At the first follow-up, women who had high-dose chemotherapy reported significantly worse physical function, role function, social function, fatigue, dyspnea, and global quality of life.

At the 6-month and 9-month follow-ups, these women also reported worse dyspnea, bruising, and bleeding than women who had standard-dose chemotherapy.

“We could not identify any subgroup that derived greater benefit with high-dose chemotherapy than with standard-dose chemotherapy.”

“On the basis of our results,” the investigators conclude that there is “no role for high-dose chemotherapy requiring autologous hematopoietic stem cell transplantation in women with metastatic breast cancer outside of a well-designed, scientifically meritorious clinical trial.”

“Findings that statins inhibited the proliferation of breast cancer cells in vitro and in rodents have raised interest in whether the use of statins might decrease a woman’s risk of developing breast cancer,” Dr. Gaia Pocobelli, of the University of Washington, Seattle, and colleagues write. Conversely, other studies in which rodents were exposed to high doses of statins showed increases in several types of cancer.

The researchers identified 4179 cases of incident invasive breast cancer in women at least 50 years of age who were diagnosed between January 1995 and May 2001. The women were randomly selected from population-based cancer registries in Wisconsin, Massachusetts, and New Hampshire.

A total of 4983 controls were also randomly selected in each state, from lists of licensed drivers and Medicare beneficiaries. Structured telephone interviews were conducted to obtain information on the use of statins and breast cancer risk factors.

Overall, 7.0% of all the women ever used a statin, including 271 cases and 336 controls. The most commonly used statins included lovastatin (2.8%) and simvastatin (2.4%). This was followed by pravastatin (1.6%) and fluvastatin (1.0%).

Cases had a slightly greater mean cumulative duration of statin use than controls (4.9 years and 4.5 years, respectively), but the overall use of statins was not associated with breast cancer risk, according to the authors. They also observed no relationship between duration of use and cancer risk.

No association was observed between the use of lipophilic statins as a group (simvastatin, lovastatin, fluvastatin) or the use of the hydrophilic statin (pravastatin) and breast cancer risk.

Fluvastatin was associated with a small reduced risk of breast cancer, but this relationship may have emerged by chance, the researchers note.

Summing up, statin usage, either lipophilic or hydrophilic, was unrelated to the risk of breast cancer in middle-age women, the researchers conclude. However, given the extensive use of these agents, they suggest that further investigation of individual statins is warranted.

Screening rates from 2001 through 2004 were nearly 11 percent lower for women who had to contribute a co-pay as low as $12, compared to women whose breast X-rays were free, researchers from Brown and Harvard universities found.

They surveyed more than 366,000 women aged 65 to 69.

“I think it’s a surprising result,” said Dr. Amal Trivedi of Brown, who led the study. “Most people would consider $12 to be a rather modest sum. But when it came to this population, co-payments as low as $12 led to a very sharp decrease in the breast cancer screening rate.”

Studies have suggested that mammograms may save lives by detecting breast cancers at an earlier, and more curable, stage. “This is a case where co-payments adversely affected health,” Trivedi said in a telephone interview.

Breast cancer is more difficult — and more expensive — to treat at its later stages.

“It would make clinical sense, and probably economic sense, for a health plan to eliminate a co-payment for a mammogram,” Trivedi said.

Breast cancer was diagnosed in 178,000 U.S. women in 2007, and killed more than 40,000, according to the American Cancer Society, which recommends regular mammograms for women over 40.

The researchers found that mammography rates were about 4 percent lower for women living in areas where the people were poor or poorly educated, if they were required to pay part of the cost. Most plans require a $20 co-payment.

In 2001 only one woman in 200 was required to make a co-pay for a mammogram. By 2004 the ratio was 1 in 9.

The researchers reported in the New England Journal of Medicine that when patients were suddenly required to foot part of the bill, screening rates declined by 5.5 percentage points even as the rates among women in plans that continued to pay the full cost increased by 3.4 percentage points.

Dr. Peter Bach of the Memorial Sloan-Kettering Cancer Center in New York said the study “tests a fundamental presumption of the high-deductible movement — that a knowledgeable consumer will make wise decisions when purchasing health care.”

But even though nearly all women know the value of mammograms, many did not get them when they had to pay.

“The findings suggest that the introduction of a small out-of-pocket expense led 8 percent of consumers to opt out of mammography — a decision that, on average, was not in the best interest of their health,” Bach wrote in a commentary.

Data from women in 174 Medicare managed-care plans in 38 states was used for the study. These plans represent one in sixMedicare recipients. “It’s reasonable that our findings would extend to people beyond this selected group,” Trivedi said.

The Agency for Healthcare Research and Quality considers radiotherapy after breast conservation surgery (BCS) as a quality of care indicator, yet many do not receive this treatment, comment Dr. Dawn L. Hershman and colleagues from Columbia University in New York. The goal of the present study was to determine whether surgeon-related factors play a role in the receipt of post-BCS radiotherapy.

To do this, the researchers analyzed data from 29,760 women, aged 65 years or older, who underwent BCS for stage I/II breast cancer from 1991 and 2002 and were entered in a Surveillance, Epidemiology, and End-Results-Medicare linked database. Surgeon characteristics were assessed using information in the American Medical Association Masterfile.

Overall, 75% of the women received adjuvant radiotherapy, the report indicates. Women given radiotherapy were younger, had fewer comorbidities and were more often white, married, from an urban area, and were typically diagnosed in a later year than those not treated with radiotherapy.

Patients given radiotherapy were more likely to have a female surgeon (79% vs. 73%), one with an MD rather than DO degree (75% vs. 68%), and one who trained in the US rather than elsewhere (75% vs. 70%). Having a surgeon with 15 or more patients also raised the likelihood of receiving radiotherapy.

“Our study is one of the first to demonstrate associations between certain surgeon characteristics and quality of breast cancer care,” Dr. Hershman and colleagues conclude. “If confirmed, more research is needed on whether they reflect surgeon behavior, patient response, or physician-patient interactions.”

Dr. Margaret A. Olsen of Washington University School of Medicine, St. Louis and colleagues retrospectively studied 949 women who underwent mastectomy or breast reconstruction procedures between 1999 and 2002 at a hospital affiliated with Washington University.

They found that 50 women (5.3%) developed surgical site infections during the original surgical admission or within 1 year of surgery. The average time between surgery and diagnosis of infection was 46.6 days.

“Surgical site infection after breast cancer surgical procedures was more common than expected for clean surgery and more common than surgical site infection after non-cancer related breast surgical procedures,” the investigators report.

The incidence of surgical site infection was 12.4% following mastectomy with immediate implant reconstruction, 6.2% following mastectomy with immediate reconstruction using a transverse rectus abdominis myocutaneous flap, 4.4% following mastectomy only, and 1.1% following breast reduction surgery.

Dr. Olsen and colleagues also found that women who developed a surgical site infection had significantly longer hospital stays and significantly higher hospital costs compared with those who did not.

After adjusting for the type of surgery performed, breast cancer stage and other factors that influence cost, hospital-associated costs of surgical site infections were $4,091 per patient. As this figure does not include physician costs or costs incurred due to extra clinic visits, outpatient procedures, outpatient antibiotic use or home health care, it likely represents “at best, the minimum costs associated with serious surgical site infection,” the investigators point out.

“Interventions to reduce the incidence of surgical site infection following breast cancer surgical procedures are essential to reduce not only morbidity in these patient populations but also costs to the individuals and society,” Dr. Olsen and colleagues conclude.

Earlier reports have indicated that radiotherapy regimens used in the 1970s elevate cardiovascular risk, but it has been less clear if more recent regimens also increase the risk.

“Apart from the clear benefits of adjuvant radiotherapy, physicians should still be aware of the potentially increased risk of cardiovascular disease following specific radiotherapy regimens in long-term breast cancer survivors,” senior author Dr. Flora E. van Leeuwen, from the Netherlands Cancer Institute in Amsterdam, and colleagues note.

To investigate, the researchers evaluated 4414 breast cancer patients who survived for 10 years after treatment radiotherapy between 1970 and 1986. The rates of cardiovascular disease in these patients were compared with those seen in the general population.

A total of 942 cardiovascular events were logged during a median follow-up period of 18 years, yielding a standardized incidence ratio of 1.30.

Radiotherapy limited to the breast did not increase the risk of cardiovascular disease. Inclusion of the left or right internal mammary chains, however, did increase the risk.

Internal mammary chain radiation in the 1970s appeared to increase the risk of myocardial infarction and congestive heart failure by 2.55- and 1.72-fold, respectively, compared with no radiation. By contrast, radiotherapy in the 1980s did not raise the risk of myocardial infarction, but was associated with 2.66- and 3.17-fold increased risks of heart failure and valvular dysfunction, respectively.

In the 1980s, adding adjuvant chemotherapy to radiotherapy increased the risk of congestive heart failure by 1.85-fold. Moreover, a 3-fold increased risk of myocardial infarction was seen radiotherapy-treated patients who also smoked.

In a related editorial, Dr. Sharon H. Giordano and Dr. Gabriel N. Hortobagyi, from the M.D. Anderson Cancer Center in Houston, comment that the study “provides important new information on the cardiac toxicity of radiation therapy.”

They also praise the study’s methodology, calling the 18-year follow-up period “impressively long” and citing certain unique features, including evaluation of both morbidity and mortality, and comparison of toxicity by radiation fields.

The interim results of the HIBCRIT (High Breast Cancer Risk Italian Trial) are reported by Dr. Francesco Sardanelli of the University of Milan and associates in the March issue of Radiology.

These findings demonstrate that “the addition of MR imaging to the screening regimen for high-risk women may enable detection of otherwise unsuspected breast cancers,” Dr. Sardanelli said.

Dr. Sardanelli’s group examined the results for 278 women who underwent breast cancer screening by clinical breast examination, mammography, ultrasonography and contrast material enhanced MR imaging.

The women were BRCA1 or BRCA2 mutation carriers, first-degree relatives of BRCA1 or BRCA2 mutation carriers, or had a strong family history of breast or ovarian cancer.

Breast cancer was found in 11 of the 278 women in the first round of screening by all procedures and in 7 of 99 women in the second screening round. In 6 of these 18 patients (33%), cancer was detected only by MR imaging.

There was a “negative clinical breast examination, mammography and ultrasound,” continued Dr. Sardanelli. “This confirms the role of MR imaging in the surveillance of high-risk women.”

“On the other hand,” he pointed out, “it’s important to note that these results cannot be translated to average-risk women. In other words,” he concluded, “breast MR imaging can be considered as a screening tool only for high-risk women.”

“In the subgroup of patients with HER2-positive, high-risk breast cancers, trastuzumab enhances the clinical advantage of adjuvant chemotherapy at a cost generally considered appropriate for the added value that trastuzumab produced,” Dr. Nicola Lucio Liberato, lead author of the first study, said in a statement.

Dr. Liberato, from Ospedale Civile “C. Mira” in Pavia, Italy, and colleagues used a Markov model to asses the cost-effectiveness of 12-month trastuzumab adjuvant therapy in women with high-risk HER2-positive early breast cancer. Probabilities of disease recurrence and survival were derived from the National Surgical Adjuvant Breast and Bowel Project B-31 and other trials.

Adjuvant therapy with trastuzumab increases life expectancy by 1.54 quality-adjusted life years (QALYs) in the target patient group, the report indicates. The cost per life-year saved was between 14,861 and 18,970 euros, which is on par or lower than the costs associated with other adjuvant therapies.

In the second study, Dr. Allison W. Kurian, from Stanford University School of Medicine in California, and colleagues used a Markov model to compare the cost-effectiveness of chemotherapy alone, an anthracycline-based regimen plus trastuzumab, and a non-anthracycline regimen plus trastuzumab.

The authors found that the anthracycline-based therapy plus trastuzumab carries an incremental cost-effectiveness ratio of $39,982 per QALY, a cost that compares favorably with that of other therapies for early breast cancer. The non-anthracycline-based trastuzumab regimen was less effective and more costly.

If the trastuzumab fails to provide benefit after 4 years of treatment, the incremental cost-effectiveness ratios of each trastuzumab regimen exceed $100,000 per QALY.

“Some people may be surprised” by the results, Dr. Kurian said in a statement. “Our findings show that in a specific treatment situation — early in the course of the disease — even an expensive therapy like trastuzumab can provide large enough health benefits that it represents a good value.”

Tykerb (lapatinib) is a tyrosine kinase inhibitor of HER2 and epidermal growth factor receptor. It blocks the intracellular HER-2/neu protein, whereas Herceptin (trastuzumab) blocks HER-2/neu on the outside of cancer cells.

The drug was approved for once-daily use in combination with Roche’s oral chemotherapy drug Xeloda, or capecitabine, Glaxo spokeswoman Mary Anne Rhyne said.

Drinking just over two drinks daily may increase their breast cancer risk by 32 percent, Dr. Shumin M. Zhang of Harvard Medical School in Boston and colleagues found.

“Moderate alcohol consumption increases your risk of breast cancer,” Zhang said “If you drink alcohol, you should think about the risks and benefits, there is a risk definitely.”

Beer, liquor, and white wine all conferred increased risk, but not red wine. Zhang said it’s possible chemicals in red wine such as resveratrol and other polyphenols could counteract the harmful effects of alcohol. But, she added, the findings don’t prove red wine is safe.

A number of studies have linked moderate alcohol consumption to an increased risk of breast cancer, Zhang and colleagues point out in a report in the American Journal of Epidemiology. They set out to determine if the type of tumor might influence this relationship. Most breast cancer tumors contain receptors for both estrogen and progesterone, while some have receptors for just one of the hormones or for neither.

The researchers followed 39,876 women participating in the Women’s Health Study. During the 10-year follow up period, 1,190 developed invasive breast cancer and 294 were diagnosed with early-stage disease.

Women who consumed 10 grams of alcohol a day — between three-quarters of a drink and one drink — were at 7 percent greater risk of developing breast cancer, and at 9 percent greater risk of developing more advanced disease. Among those who drank 30 grams of alcohol daily, overall risk of breast cancer rose 32 percent, and 43 percent for invasive disease.

The increased risk was most substantial for women who had tumors carrying both estrogen and progesterone receptors, who represented about two-thirds of all breast cancer cases.

Alcohol is thought to affect breast cancer risk by influencing estrogen levels, and the finding that the link was strongest among women with estrogen- and progesterone-receptor positive tumors backs up this hypothesis, Zhang notes.

Women who were taking postmenopausal hormones also showed a greater risk; those who drank 10 grams of alcohol daily and were on hormone therapy were 84 percent more likely to develop breast cancer than those who didn’t drink and weren’t taking hormones.