Chemotalk Newsletter

Chemotalk Newsletter, Vol. 81: January 1, 2015

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End of the year, but the fight continues.

Happy New Year!  Here we go ....


An analysis of a large number of women suggested that those who use bisphosphonates, a bone medication used to treat osteoporosis and other bone loss diseases, have a reduced risk of ENDOMETRIAL CANCER. The results were published in Cancer, a peer-reviewed journal of the American Cancer Society.

Sharon Hensley Alford, PhD, of the department of public health sciences at Henry Ford Health System in Detroit, and colleagues used self-reported questionnaires that were part of the National Cancer Institute¹s Prostate, Lung, Colorectal and Ovarian (PLCO) Cancer Screening Trial to test the hypothesis that bisphosphonates may mitigate the risk of endometrial cancer.

After accounting for factors such as age, race, history of hormone therapy use, smoking status, and body mass index in the 23,485 women included in the analysis, those who were bisphosphonate users were half as likely to develop endometrial cancer (incidence rate ratio of 0.489). There were 77 cases of endometrial cancer in the group who never used bisphosphonates and 20 in the user group. Sixty-nine and 19 cases in the never-user and user groups, respectively, were type I endometrial tumors.

Ninety-two percent of the women included in the study were white non-Hispanic women, suggesting that the effect of bisphosphonates on African-American and Hispanic women needs to be studied further. Another limit of the study is whether bisphosphonates affect type I and type II endometrial tumors in the same way, since the vast majority of cancer incidences were type I tumors.

"Other studies have shown that bisphosphonates may reduce the risk of certain cancers, but we are the first to show that the risk for endometrial cancer may also be reduced," said Alford in a statement. "This study suggests that women who need bone strengthening medications and who have increased risk for endometrial cancer may want to choose the nitrogen form of bisphosphonates because this form may reduce the risk of endometrial cancer."

The study analyzed data only on certain bisphosphonates‹those that contain nitrogen, which have been shown to have anticancer properties. These agents are also used as a palliative treatment for patients with bone metastases. There is preclinical evidence that these drugs have anti-tumor effects, including inhibiting proliferation, angiogenesis, and adhesion of tumor cells. In the laboratory, bisphosphonates have also been shown to alter the tumor microenvironment and induce tumor cell death

Bisphosphonates are currently being studied in the clinic as agents that could prevent disease progression or metastasis, but their role as chemopreventive agents has not been well explored. "It is now clear that these drugs, particularly those that contain nitrogen, also affect tumor cells," wrote the authors.

Endometrial cancer is typically diagnosed in postmenopausal women in their 60s and 70s, at the time of decreasing bone density. It accounts for almost 50% of gynecologic cancers diagnosed in the United States, and is the fourth most common cancer in women.

"Additional studies are needed that include other potential confounders and a larger sample so that type II endometrial cancer could be assessed more confidently. A randomized trial in postmenopausal women that assessed endometrial, breast, and colorectal cancer would be ideal," concluded the authors.

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A retrospective cohort study of more than 1.2 million women treated for early-stage breast cancer in the United States has confirmed rising trends in the proportion of patients who undergo mastectomy, bilateral mastectomy, and breast reconstruction rather than breast conservation surgery for which they are eligible. Findings were reported in JAMA Surgery by Kristy L. Kummerow, MD, of the division of surgical oncology and endocrine surgery, and colleagues at the Vanderbilt University Medical Center and Tennessee Valley Healthcare System, Nashville, Tennessee.

Breast conservation surgery was endorsed by the National Institutes of Health Consensus Conference in 1990 after studies demonstrated equivalent outcomes with mastectomy in early-stage breast cancer, "and has become a standard of excellence in breast cancer care," noted the authors. Accredited breast centers in the United States are thus measured on performance of breast conservation surgery in more than 50% of women who are eligible.

All participants in the study were treated at centers accredited by the American Cancer Society and the American College of Surgeons Commission on Cancer from January 1, 1998, to December 31, 2011, using the National Cancer Data Base. The study was designed to determine the proportion of women with early-stage breast cancer who underwent mastectomy. Secondary outcome measures included temporal trends in breast reconstruction and bilateral mastectomy for unilateral disease.

A total of 64.5% of patients underwent breast conservation surgery while 35.5% underwent mastectomy. Those who underwent breast conservation surgery differed from those who underwent mastectomy by demographic and tumor characteristics. The mastectomy group included fewer racial and ethnic minorities. Mastectomy was more likely to be performed in women with more comorbid conditions; those with managed care, Medicare, or no insurance; women treated in the South or in areas with a lower educational level; and in women whose tumors were invasive (versus in situ), larger, less differentiated, or associated with clinically positive nodes.

Among patients treated with mastectomy, 45% underwent total mastectomy, 34.7% had modified radical mastectomy, 19.5% had bilateral mastectomy, and 0.8% had radical mastectomy, the investigators reported. "The proportion of breast conservation surgery­eligible women who underwent mastectomy increased from 34.3% in 1998 to 37.8% in 2011 (P < .001 for trend). In the general multivariable model for the most recent 8 years, the odds of mastectomy increased 34% by 2011 relative to 2003 (odds ratio = 1.34; 95% CI, 1.31-1.38), with the most notable rise in mastectomy rates occurring after 2006."

Temporal trends were similar for the secondary outcomes, with notable increases in the proportion of women who underwent breast reconstruction and bilateral mastectomy starting in the mid-2000s, with a continued increasing trend over time. Breast reconstruction in women undergoing mastectomy rose dramatically from 11.6% in 1998 to 36.4% in 2011, noted the authors. Bilateral mastectomy for unilateral disease increased from 1.9% of breast conservation surgery-eligible women in 1998 to 11.2% in 2011. And bilateral mastectomy increased from 5.4% in 1998 to 29.7% in 2011 among women undergoing any type of mastectomy for unilateral disease. Reconstruction was performed in 57.2% of women who underwent bilateral mastectomy in 2011 compared with 36.9% in 1998.

Although the increase in bilateral mastectomy in unilateral disease is not well understood, the authors noted that qualitative studies suggest that physician recommendation, patient concern about recurrence, increased use of breast magnetic resonance imaging (MRI), and desire for symmetry are the main reasons women opt to undergo bilateral mastectomy. Multiple factors are involved when physicians and patients decide how to surgically manage an individual breast cancer case, the authors continued, citing a study on decision-making in patients with early-stage breast cancer that demonstrated greater discordance between patient goals and ultimate surgical treatment in women who underwent mastectomy than in those who underwent breast conservation surgery. "Furthermore, less than 50% of women reported being asked by their physicians whether they preferred breast conservation surgery or mastectomy, and more than 80% of women reported that their physicians made a specific recommendation for either breast conservation surgery or mastectomy."

Findings of the present study have "implications for physician and patient decision-making as well as quality measurement," the investigators concluded. ³Further research is needed to understand patient, provider, policy, and social factors associated with these trends.²

Commenting on the findings, Mehra Golshan, MD, director of breast surgical services at Dana-Farber/Brigham and Women¹s Cancer Center, Boston, said, "This study adds to the literature that is already out there on the subject. We have seen an increase in our prophylactic mastectomy rates and also for women who are eligible for breast conservation, to the mastectomies, including bilateral mastectomy, for almost a decade now. This is a trend that is in contrast to almost every other area in surgery where we¹ve gone toward the less invasive, whether it¹s robotic, laparoscopic, endoscopic‹it¹s always less rather than more invasive. And we¹ve known for many years that mastectomy and breast conservation give the same outcomes for most women with early-stage breast cancer in terms of survival. The trend is disturbing but it has been known for awhile and a lot of people are looking at factors."

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By Andrew Pollack

Drugs that free the body's immune system to fight cancer have shown strong preliminary results in treating HODGKIN'S LYMPHOMA, shrinking tumors in well over half of patients who had exhausted many other treatment options, researchers reported.

The drugs have already generated great excitement because of their strong early results on various so-called solid tumors particularly MELANOMA but also LUNG CANCER, KIDNEY CANCER and some others.  The results represent the strongest evidence to date that the medicines, known as PD-1 inhibitors, also have promise for at least some of the so-called liquid tumors of the blood and bone marrow.

In a small study, the drug nivolumab significantly shrank tumors in 20 of 23 patients, or 875, with Hodgkin's lymphoma.  Four of the 23 patients, or 17%, had a complete response, meaning the total or near total disappearance of tumors.

The drug pembrolizumab shrank tumors in 66% of 29 patients with Hodgkin's, with 21% having a complete response.

Both studies were Phase 1 trials designed mainly to test safety so it is too early to say how effective the drugs will ultimately be or whether they will prolong lives.

The results were presented in San Francisco at the annual meeting of the American Society of Hematology.  The nivolumab results were also published by The New England Journal of Medicine.

There will be about 9,200 new cases of Hodgkin's lymphoma in the United States this year and 1,200 deaths, according to the American Cancer Society. The illness, also known as Hodgkin lymphoma or Hodgkin's disease commonly affects young adults.  Many are essentially cured but about 30% either do not respond to initial treatment or eventually have a relapse.

Dr. Philippe Armand of the Dana-Farber Cancer Institute, who presented the nivolumab results at a news conference, and Dr. Craig H. Moskowitz of the Memorial Sloan Kettering Cancer Center, who presented the pembrolizumab results, said the preliminary findings were very encouraging because the patients had pretty much exhausted other options like CHEMOTHERAPY, the relatively new drug Adcetris - also known as brentuximab vedotin - and stem cell transplants.

It is not yet clear how long the effects of the drugs will last, they said, but in the nivolumab trial, 86% of the patients experienced no worsening of disease for at least six months.

The drugs can cause some severe side effects, including inflammation of the pancreas, lung or colon, but the investigators said these were rare.  In the nivolumab trial, five patients, or 22%, had a serious side effect.

Both drugs block the action of PD-1, which acts as a brake on the immune system.  Many tumor cells activate this brake by making a protein called PD-L1, which binds to PD-1 on immune cells.  By blocking PD-1, the drugs release the brake and allow the immune system to work.

Hodgkin's lymphoma was thought to be particularly susceptible to these types of drugs because its cells have a genetic abnormality that leads to a production of large amount of PD-L1.

So the drugs might not work as well for blood cancers that lack this genetic vulnerability.  For the more common non-Hogkin's lymphoma, nivolumab shrank tumors significantly in roughly 30% of patients, according to other results being presented at the conference.

The drug with the brand name Keytruda won approval from the Food an Drug Administration in September as a treatment for certain patients with advanced melanoma.  Opdivo was approved in Japan for melanoma and is under review for that use by the F.D.A.

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This is a short newsletter.  I promise to make up for it next month. There's definitely enough to talk about...

And if you have any thoughts of how this newsletter could be improved, please email me directly, at

Elaine Jesmer

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