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.”

Recent evidence suggests that androgen suppression therapy increases the risk of cardiovascular events in men of advanced age, lead author Dr. Anthony V. D’Amico of Brigham and Women’s Hospital in Boston and his associates note.

To examine the interaction between comorbidity and treatment outcome, they obtained long-term follow-up data from a trial in which men with prostate cancer had been randomly assigned to receive radiation therapy alone or radiation therapy and androgen suppression therapy combined.

The study included 206 patients, median age 72.5 years, with localized prostate cancer and at least one of four unfavorable prognostic factors – PSA > 10 ng/mL, a biopsy Gleason score of 7-10, extracapsular extension, or seminal vesicle invasion. At baseline between 1995 and 2001, subjects were randomized to external beam radiation therapy alone or in combination with 6 months of androgen suppression therapy.

The authors determined comorbidity scores based on the severity of several clinically relevant ailments present at baseline.

Seventy-four men died during median follow-up of 7.6 years. For the group as a whole, the risk of all-cause mortality was significantly increased in the radiation therapy group (44 vs 30 deaths, hazard ratio 1.8, p = .01).

“However, the increased risk in all-cause mortality appeared to apply only to men randomized to radiation therapy with no or minimal comorbidity” (31 vs 11 deaths; HR 4.2, p < .001), Dr. D’Amico’s team reports.

For those with moderate or severe comorbidity, mortality rates did not differ significantly between treatment groups (13 vs 19 deaths, HR 0.54, p = .08).

“The clinical significance of this finding is that preexisting comorbid illness may increase the negative effects of specific anticancer treatments such as androgen suppression therapy,” Dr. D’Amico and his associates suggest.

As their study was a hypothesis-generating, post-randomization subgroup analysis, they recommend the findings be verified in a clinical trial specifically designed to assess the interaction of comorbidity with androgen suppression therapy treatment.

Furthermore, they add, studies should be designed to identify the impact of specific comorbid illnesses on life expectancy and health-related quality of life.

“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.

To examine the effects of race and ethnicity on tumor characteristics and outcomes, Dr. Steve R. Martinez, of University of California at Davis Cancer Center in Sacramento, and colleagues used the Surveillance, Epidemiology, and End Results (SEER) database to identify 6406 patients with extremity soft-tissue sarcoma treated between 1988 and 2003. Included were 4636 whites, 773 blacks, 696 Hispanics, and 411 Asians.

“Hispanics tended to be diagnosed with extremity soft-tissue sarcoma at a younger age than their white, black, and Asian counterparts, which may suggest either a biologic predisposition or an environmental contributing factor for the development of these tumors,” the authors suggest.

Hispanics and blacks were less likely to receive radiation therapy than other groups, despite presentation with larger tumors. Hispanics tended to have higher rates of well-differentiated to moderately differentiated tumors, whereas blacks presented with more poorly differentiated or undifferentiated tumors.

“Hispanics, although they are subject to several of the same socioeconomic factors and exhibit several of the same poor tumor prognostic factors and comorbidities as blacks, displayed a disease-specific survival that, although not significantly superior to whites, clearly trended in that direction,” the investigators report.

There is no simple explanation for the racial and ethnic differences observed in treatment outcomes in patients with primary extremity soft-tissue sarcoma, the researchers state. Genetics, sociodemographics, and access to specialty care all likely play a role.

“The identification of disparities represents a unique opportunity to improve care by addressing the issues leading to the disparities,” Dr. Martinez said.

“Extremity soft tissue sarcomas are rare and can be difficult to diagnose,” he added. “If possible, patients should be referred to a nearby Cancer Center or center of excellence where patients can be treated by a multidisciplinary team of experts.”

“We are going to narrow our focus to identify potential genetic or epigenetic explanations for the differences in survival noted in this study,” Dr. Martinez said. “In other words, are the survival differences between racial/ethnic populations due to the fact that these populations have, on a genetic and epigenetic level, very different diseases?”

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.

“To offer the patient a better evaluation of his prostate gland, the physician should perform the DRE as well as the PSA test,” Dr. William J. Catalona from Northwestern University Feinberg School of Medicine, Chicago, said.

Dr. Catalona and colleagues compared clinical variables and survival outcomes between patients diagnosed with prostate cancer by DRE alone versus those diagnosed by PSA level, regardless of DRE findings.

Of 2233 men who were diagnosed with prostate cancer and underwent radical prostatectomy, 303 (14%) were diagnosed on the basis of DRE alone, 1426 (64%) on the basis of PSA alone, and 504 (22%) based on abnormalities of both tests, the authors report.

Eighteen percent of men who underwent a prostate biopsy because of abnormal DRE findings alone were diagnosed with prostate cancer.

Twenty percent of cancers detected by DRE alone were nonorgan-confined, 20% had a Gleason score of 7 or higher, 16% had positive surgical margins, 3% had seminal vesicle invasion, and 1.3% had lymph node metastases.

Adverse pathology was significantly more likely in men with abnormalities in both DRE and PSA than in those detected by either test alone, the researchers say.

Ten-year progression-free survival was similar for cancers detected by DRE only (83%) or PSA only (82%), but significantly lower for cancers detected by abnormalities in both DRE and PSA (63%), the investigators note. Similar results were seen for overall survival and cancer-specific survival.

“Eliminating DRE from screening protocols would miss a significant proportion of patients with a clinically important and potentially curable prostate cancer,” the authors conclude.

However, “it may be reasonable to avoid DRE in men with a PSA level less than 1 ng/mL,” they add.

“PSA testing and DRE must be continued on a regular (annual) basis to be most effective, and persistent changes over time are as important as the absolute findings at any one point in time,” Dr. Catalona said.

“Research has shown that patients who are enrolled in clinical trials offering the most advanced cancer treatments do better than patients who receive conventional treatment,” lead author Dr. Peter H. Shaw, from the Children’s Hospital of Pittsburgh, said in a statement.

He added that there are two main reasons why clinical trial access is more limited for adolescents and young adults than for children. First, adolescents and young adults are often treated by adult oncologists at centers that are not participating in trials geared toward pediatric malignancies. Second, at the national level, there are simply far fewer clinical trials of cancers affecting adolescents and young adults compared with those affecting younger patients.

The findings are based on analysis of data for all patients who were diagnosed with a new malignancy at the researchers’ center between July 2001 and June 2006. The study group included 501 patients younger than 15 years old and 139 between 15 and 22 years old.

Thirty-six percent of the subjects participated in a clinical trial, which included 38% of the younger patients and 27% of the adolescents and young adults (p = 0.03). Trial unavailability accounted for non-enrollment of 57% and 41% of patients in the older and younger age groups, respectively (p = 0.04).

“We hope (this study) drives home the point that these teen and young adult oncology patients need to be seen at children’s hospitals to have access to the most up-to-date treatments and even then, we as pediatric oncologists have to make more studies available to them for better care,” Dr. Shaw said.

He added that future research needs to “address which diseases are under-represented in the clinical trial realm.”

MiRNAs are small (19-25 nucleotides long), non-coding RNAs that down-regulate gene expression. Their expression has been linked over the past 5 years or so to hematopoiesis and to cancer in both humans and mice.

The first report associating miRNAs and cancer involved chronic lymphocytic leukemia. Because of the specific mechanisms causing AML, and because patients with AML often have a relatively poor prognosis, creating a need for novel therapies, the researchers attempted to determine whether miRNAs are associated with cytogenetic abnormalities and clinical features in AML.

Dr. Ramiro Garzon of Ohio State University in Columbus and colleagues obtained bone marrow and blood samples from 182 untreated patients newly diagnosed with AML. Using a microarray system, the researchers analyzed the miRNA expression in 122 of these AML samples; the other 60 pretreatment samples were used to validate the miRNA signatures with quantitative real-time PCR. (A second cohort of 54 patients with relapsed or refractory AML was also evaluated.)

The researchers found a “distinct spectrum” of miRNA expression in the AML patients versus normal CD34+ progenitor cells, identifying 26 down-regulated miRNAs and none that were up-regulated. PCR testing of seven miRNAs validated all but one.

“Similar miRNAs signatures to those of the untreated patients were obtained” from the relapsed/refractory AML patients, the researchers wrote, “thereby supporting the hypothesis that miRNA expression is largely driven by cytogenetics.”

Elderly patients with metastatic colon cancer are generally excluded from randomized clinical trials, but were included in the OPTIMOX1 trial, led by Dr. Arie Figer of Beth Sourasky Medical Center in Tel Aviv, Israel. OPTIMOX1 was an evaluation of FOLFOX7, a simplified leucovorin (LV) and 5-fluorouracil (5FU) regimen (sLV5FU2) with high-dose oxaliplatin, in a new oxaliplatin stop-and-go strategy.

The study included 620 previously untreated patients between 76 and 80 years of age with metastatic colon cancer who were randomized to one of two arms of treatment.

One group received FOLFOX4, consisting of leucovorin followed by a bolus of 5-fluorouracil (5FU) and a 22-hour infusion of 5FU and oxaliplatin on day 1 every 2 weeks, which was given until disease progression occurred.

The other group received FOLFOX7 for six cycles, followed by 12 cycles of oxaliplatin and then reintroduction of FOLFOX7. FOLFOX7 consisted of leucovorin, followed by a 46-hour infusion of 5FU and oxaliplatin started on day 1 every 2 weeks.

Dr. Figer and colleagues report in the December 15 issue of Cancer that “the overall response rate was 59.4%, comparable to younger patients (59%).”

“Median progression-free survival was 9.0 months and median overall survival was 20.7 months. These results did not differ from that in patients 75 years and younger in the OPTIMOX1 study,” the investigators report.

The older patients had more grade 3/4 toxicity than younger patients, at 65% and 48%, respectively. This consisted primarily of more neutropenia, occurring in 41% of older patients and 24% of younger patients, and neurotoxicity, occurring in 22% of older patients compared with 11% of younger patients.

“Tolerability, however, was manageable and no toxic death occurred in this elderly population,” the investigators report.

They assert that “performance status and geriatric assessment are surely better criteria than age to predict the efficacy and toxicity of chemotherapy.” In older patients deemed able to tolerate FOLFOX, this stop-and-go oxaliplatin management plan can be offered.

“Fertility preservation is a rapidly developing field, and it is important that the different available options for fertility preservation be known worldwide for every woman facing cancer treatment,” Dr. Shai E. Elizur from McGill Reproduction Center, Royal Victoria Hospital, Montreal, said. “Young women facing gonadotoxic treatment should be referred as soon as possible to a fertility specialist to consider fertility preservation options.”

Dr. Elizur and colleagues report the IVF characteristics and outcomes of 8 nulliparous women conservatively treated for well-differentiated endometrial adenocarcinoma who underwent 31 IVF cycles at Chaim Sheba Medical Center, Rabin Medical Center, or Laniado Hospital, all in Israel.

Compared with their total IVF population, the authors report, there were significantly more cycles in the endometrial carcinoma group in which the endometrial thickness was less than 8 mm, and none of the women in this group had endometrial responses of more than 10 mm (compared with 43.8% of IVF cycles in the total IVF population with endometrial thickness above 10 mm).

The fertilization rate of 58.6% in this group did not differ from the overall IVF population, the report indicates, and 6 of the 8 women (75%) conceived.

The pregnancy rates were 28% per cycle and 29.2% per transfer, the investigators say, and 4 women delivered 6 healthy offspring.

Three women experienced a recurrence of endometrial carcinoma within 18 to 44 months, the researchers note, but all were successfully retreated.

“Since hormonal treatment for endometrial cancer is still experimental, we follow these patients very closely by repeated endometrial samplings every 3-6 month,” Dr. Elizur said. “We would recommend definitive surgical treatment when the woman completed her family planning.”

“In vitro fertilization is probably a reasonable treatment option, because it will shorten the interval from the conservative to definitive cancer treatment along with offering the opportunity to cryopreserve embryos for future use combined with surrogacy,” the authors conclude.