In postmenopausal diabetic women, metformin use was associated with lower estrogen receptor—positive (ER ) and progesterone receptor–positive (PR ) breast cancer incidence, according to data presented at ASCO.

	“Metformin is a biaguanide used in management of type 2 diabetes, in which it improves insulin resistance and may improve clinical outcomes,” said Rowan T. Chlebowski, MD, PhD, chief of Medical Oncology/Hematology at the David Geffen School of Medicine, University of California, Los Angeles, and lead author of the study. “Preliminary evidence suggests that metformin may decrease breast cancer risk by decreasing insulin levels and reducing cell proliferation.”

	Metformin helps reduce low-density lipoprotein cholesterol and triglyceride levels, and is not associated with weight gain. As such, the drug is commonly used as a first-line treatment for type 2 diabetes, particularly among overweight and obese patients with normal kidney function.

	Chlebowski and his fellow researchers measured associations between metformin use and breast cancer incidence by hormone receptor status in diabetic patients in the Women’s Health Initiative (WHI). The WHI is a multicomponent study designed to address determinants of major chronic disease in women.

	The researchers’ cohort consisted of 156,229 postmenopausal women aged 50-79 years. A total of 9277 medication-treated cases of diabetes were identified in the cohort and followed for an average of 11.1 years (SD, 3.5 years). Information on drugs taken for diabetes was collected at baseline and after 3 years of follow-up. A subgroup of 2963 women were identified as being treated with metformin.

Positive Metformin Effects Not Surprising

	Metformin, an affordable diabetes medication with a low risk of side effects, is now being considered for treatment in ER /PR breast cancer. The evidence that ER /PR breast cancer patients with lower insulin levels have improved outcomes arrives from a study presented at ASCO. The population group consisted of 156,229 postmenopausal women, of whom 2963 were women with diabetes treated with metformin.

	Metformin works by decreasing the insulin level in the body. Another way to decrease insulin levels is with healthy eating, exercising, and maintaining a healthy weight, which also reduces the risk for breast cancer and recurrence. So it’s not totally surprising that metformin use is linked with decreased ER /PR breast cancer occurrence. Continued research is needed to determine when to potentially prescribe metformin, along with specific dosage details.

	According to Chlebowski, there were major imbalances between the populations with and without diabetes.

	“The diabetics were significantly older and were more likely to be African American, certainly less likely to be physically active than the cohort as a whole, and had a tremendous difference in body mass index [BMI]: 58.6% had a BMI greater than 30,” he said.

	Among the entire study population, 8572 women had breast cancer, with 6994 cases of invasive breast cancer. Among women with diabetes, 502 had breast cancer, with 422 cases of invasive breast cancer. In the metformin subgroup, there were 174 patients with breast cancer.

	On the basis of hormone receptor status, postmenopausal women with diabetes had a 15% lower incidence (hazard ratio [HR] = 0.85; 95% confidence interval [CI], 0.72-1.00; 

 =.04) of ER /PR breast cancer compared with women without diabetes. Additionally, women with diabetes taking metformin had a 38% lower risk for ER /PR breast cancer compared with diabetic women on other regimens (HR = 0.62; 95% CI, 0.44- 0.87; 

	However, this relationship did not hold true for women with invasive breast cancer or for women with ER-/PR , ER-/PR- breast cancer. Breast cancer incidence was also not observed to be lower with triple-negative status, HER2 status, and tumor size and stage, according to Chlebowski.

	In discussing these data, Pamela J. Goodwin, MD, of Mount Sinai Hospital and Princess Margaret Hospital in Toronto, Canada, noted that there have been a number of observational studies of metformin and breast cancer risk, although none have reported details of breast cancer characteristics.

	“Energy balance, as reflected by obesity, diabetes, and its treatment are important endogenous ‘host’ factors that may influence cancer risk and progression,” she stated. “I think as we study these associations, it’s important to be aware of a time course of hyperinsulinemia, hypoglycemia, and diabetes. The potential reversibility of these factors suggests key approaches to cancer prevention.” 

Articles

In postmenopausal diabetic women, metformin use was associated with lower ER  and PR  breast cancer incidence.

Metformin May Decrease Diabetics' Breast Cancer Risk

Patients with breast cancer who undertook yoga following radiotherapy derived physical and emotional benefits from the ancient Indian practice, according to research presented at ASCO.

	The study randomized 163 stage 0-III breast cancer patients to either yoga (n = 53), stretching (n = 56), or a wait-listed control group (n = 54). The yoga and stretching groups met 3 times a week for 6 weeks during radiotherapy.

	Patients self-reported changes in fatigue, physical function, depression, benefit finding, and spirituality. The authors also assessed cortisol slope and heart rate variability (HRV) with saliva tests and 10-minute electrocardiograms that were collected at baseline, end of treatment, and 1, 3, and 6 months’ follow-up.

	By the end of radiotherapy, the yoga and stretching groups showed marked improvements in various study endpoints compared with the control group. The results were calculated as change scores:

		Changes in fatigue: yoga (-0.23, for a reduction), stretching (-0.45, for a reduction), wait-list control (0.52, for an increase), 

		Increase in physical function: yoga (5.8 at 1 month, 6.5 at 3 months, 6.1 at 6 months), stretching (2.0, 3.4, 3.4), wait-list control (0.8, -0.2, 1.1); 

		Increase in benefit finding: yoga (3.1 at 3 months and 1.1 at 6 months), stretching (-2.5 and -3.9), wait-list control (-2.5 and -4.7); 

Yoga Facilitates Healthy Living for Patients and Survivors

	It is not surprising that yoga, as compared with stretching and usual practice (control group), improved outcomes such as decreasing fatigue, improving physical functioning, and improving cortisol levels in women with breast cancer undergoing radiation treatment. The results also demonstrated a positive, linear relationship between yoga attendance and beneficial outcomes. Additionally, no injuries or adverse events occurred.

	More researchers are turning to yoga practice as a noninvasive method to help women with breast cancer during and after their treatment. Such research allows for the development of evidence-based protocols for conducting yoga sessions in this population.

	Oncology nurses can investigate yoga classes for cancer patients and survivors that are offered in their community and recommend reputable instructors to their patients. While 3 times a week for yoga practice may seem prohibitive in terms of time and money, yoga is truly a practice for living a healthy life. Yoga transcends the physical poses, breathing practices, and respect for self in the classroom and becomes a daily practice. One’s choices for selecting food to eat, responding to a stressful situation, and taking care of oneself are practiced every day.

	You can learn more about yoga for people with cancer in the Yoga for Cancer Care blog at 

	There were no differences in scores for spirituality and depression.

	The authors also found that the cortisol slope at the end of radiotherapy was steepest for the yoga group compared with the stretching and wait-list control arms (-0.12, -0.08, -0.08, respectively; 

	Yoga has been credited with acting as a stress buffer during radiotherapy, and “what we see by the end of radiotherapy is a split, where the yoga group had the steepest cortisol slope. Blunting of the cortisol slope is actually a predictor of mortality in stage IV disease,” said Lorenzo Cohen, PhD, director of the Integrative Medicine Program in the General Oncology Department at the MD Anderson Cancer Center in Houston, Texas.

	Finally, there were significant increases in HRV from baseline to post-therapy for the yoga group (64.3 ms; 

 < .05) but not for the stretching group (5.8 ms) or the wait-list control arm (-8.1 ms).

	His group is now recruiting 600 patients for a phase III trial in which patients will be blinded to the opposite study arm (yoga vs another type of stress management). This will address criticism from the cancer community that yoga offers little more than a placebo effect, Cohen said. The followup for this study will be 1 year, and the authors also will assess economic outcomes, he added. 

Patients with breast cancer who undertook yoga following radiotherapy derived physical and emotional benefi ts from the ancient Indian practice, according to research presented at ASCO.

Yoga Benefits Patients With Breast Cancer

Breast cancer survivors who stop working during chemotherapy may face the loss of long-term employment for several years after their diagnosis, according to the preliminary findings of a Surveillance Epidemiology and End Results (SEER) registry survey presented at ASCO.

	The researchers found that missed paid work during breast cancer treatment is common. They reported that 24% of patients from a population-based sample in Los Angeles missed more than 1 month of work and 32% stopped working altogether after their diagnosis.

	The team surveyed a diverse, population-based sample of 2245 women with nonmetastatic breast cancer reported to the Detroit and Los Angeles SEER registries over a 19-month period (7/05-2/07) and merged these data to SEER.

	The patients were initially surveyed 9 months after diagnosis and again 4 years later. The survey data were then merged with SEER. The team examined patterns and correlates of paid work for a preliminary sample of 760 patients aged <65 years whose cancer did not recur using chi-squared tests and logistic regression.

	“Our principal dependent variable was long-term work loss, which we defined as working prior to diagnosis but not working four years later,” noted the study’s lead author, Reshma Jagsi, MD, DPhil, associate professor in the Department of Radiation Oncology at the University of Michigan in Ann Arbor.

Increased Survivorship Introduces Challenges

		Mercy Suburban Hospital, Norristown, PA

	Breast care management and breast cancer detection have undergone dramatic changes over the last 20 to 30 years. Survivorship has increased because women are increasingly diagnosed with early-stage disease. Treatment is focused on curing the disease and preventing relapse due to metastatic disease. According to the American Cancer Society, the overall 5-year survival rate for local/regional disease is now >80%. Additionally, women are taking better care of themselves overall through improved nutrition, exercise, and rehabilitation. All of this and the increase in technology have led to the treatment of women who are more likely to be part of the workforce.

	For some women, the diagnosis of breast cancer may impose an economic hardship because they often need to take a leave of absence from work, especially during chemotherapy treatment. This will affect not only the cancer survivor, but her entire family as well. Return to work after breast cancer is important, not only from a societal point of view, but also for the rehabilitation of the cancer survivor. Moreover, returning to or maintaining employment after a cancer diagnosis is important for survivors’ quality of life, including physical, spiritual, and emotional. It seems clear from the study presented at ASCO that further development and evaluation is needed to support women with breast cancer returning to work and the obstacles they will encounter.

	A total of 539 patients (71%) reported working prior to diagnosis. Of this group, 172 (33%) were not working 4 years later.

	The researchers univariate analysis uncovered that long-term work loss was significantly associated with chemotherapy during initial treatment (40% with chemotherapy vs 26% without), as well as those who were older, Latina, less educated, had comorbidities, or received mastectomy. Jagsi reported that tumor behavior (in situ vs invasive), marital status, and radiation receipt were not associated with work loss.

	The researchers’ multivariate analysis— controlling for age, marital status, tumor behavior, comorbidity, race, mastectomy receipt, and radiation receipt&mdash;found that chemotherapy receipt at the time of diagnosis was independently associated with work loss (odds ratio, 2.4; 

 = .004). The excess long-term work loss observed for women who received chemotherapy began soon after diagnosis: Compared with women who did not get chemotherapy, women who did were much more likely to report stopping work 2 years ago or more (34% vs 16%).

	Jagsi said that breast cancer survivors were more likely to experience long-term work loss if they were older, had 2 or more comorbidities, lacked employment support, received chemotherapy at the time of diagnosis, and they lived in Detroit as opposed to Los Angeles. She noted that most women who were not working at the time of re-interview wanted to work: 59% (97/165) reported that it was important for them to work and 27% (46/168) were actively looking for work.

	“The oncology community may wish to explore targeted employment support interventions for patients who plan to receive chemotherapy and whose jobs do not include sick leave or flexible scheduling,” said Jagsi. 

Breast cancer survivors who stop working during chemotherapy may face the loss of long-term employment for several years after their diagnosis.

Breast Cancer Survivors Vulnerable to Long-Term Work Loss

A randomized trial comparing survivorship care plans with standard oncologist discharge visits in patients with breast cancer found no differences in outcomes among the groups, according to data presented at ASCO.

	A research team led by Eva Grunfeld, MD, DPhil, Giblon Professor and director of Family Medicine Research in the Department of Family and Community Medicine at the University of Toronto, examined Recommendation 2 from the Institute of Medicine handbook 

From Cancer Patient to Cancer Survivor: Lost in Transition

, which states, “Patients completing primary treatment should be provided with a comprehensive care summary and follow-up plan that is clearly and effectively explained. This ‘Survivorship Care Plan’ should be written by the principal provider who coordinated oncology treatment.”

	Grunfeld noted that the recommendation was made for all patients because it was considered to have face validity, although there had never been a rigorous evaluation of the hypothesis.

	The multicenter study enrolled 408 patients with early-stage breast cancer who completed primary treatment at least 3 months previously (except for continued use of hormonal therapy) and without recurrent or new primary cancer. All the patients were transferred to their family practitioner (FP) for follow-up care.

Survivorship Care Study Contradicts Expectations

		The University of Kansas Cancer Center, Kansas City

	The results about survivorship care plan outcomes presented by Grunfeld et al at ASCO seem contradictory to what we hear in daily interactions with patients. Repeatedly, nurse navigators hear stories from patients lost in the shuffle and seeking to answer, “What is my roadmap once treatment ends?”

	Survivorship care plans have been sought by survivors and are intended to improve care coordination. Given this report, should we ask, “Are we communicating long-term needs in a way meaningful to the survivor?”

	Nurse navigators are key players in the successful integration of survivorship as a distinct phase in cancer care. Key to that role is preparing patients for a transition from the safety net of their oncology care providers and for achieving a lifetime of good health.

	The field of survivorship has matured in part due to the growing voice of survivors who seek patient-centered care throughout their lifetime. Rightfully so. Given the shortage of cancer specialists and increasing complexity of cancer treatments, oncologists will not be able to follow their patients long-term. The movement toward survivorship wellness will continue and be further refined not only by the medical field, but most importantly, by patients and customer demand.

	An intervention group of 200 patients received a survivorship care plan consisting of a treatment summary, a patient version of follow-up guidelines, and brochures and information about local relevant supportive care resources. These were compiled and reviewed with the patient in a 30-minute educational session with a nurse.

	The FPs of intervention patients received a copy of all documents plus the full guideline and a reminder table of recommended follow-up visits and tests.

	In the control group, 208 patients received a discharge visit and FPs received a discharge letter, according to usual practice.

	“The primary outcome was breast cancer— related psychological adjustment at 12 months post-intervention,” said Grunfeld. She added that secondary outcomes included continuity of care, health-related quality of life (SF-36), patient satisfaction, and adherence to guidelines.

	According to the researchers, there were no differences among the groups on psychosocial adjustment, or on any of the secondary outcomes studied.

	“The results of this trial do not support the hypothesis that survivorship care plans are beneficial to improve patient-reported outcomes,” Grunfeld noted. “A standard discharge visit with the oncologist achieved similar results as a comprehensive care plan and educational session.”

	Lynne I. Wagner, PhD, director of Supportive Oncology at the Robert H. Lurie Comprehensive Cancer Center of Northwestern University in Chicago and co-chair of the session in which the data were presented, said that she was surprised by Grunfeld’s findings because a survivorship care plan “seems like the right thing” to do.

	Wagner did, however, note one positive result from the study.

	“The finding in both arms of the study that the primary care physician is the correct point of contact is significant given the anticipated gap in the oncology workforce in the United States,” Wagner said. “It will become increasingly important for survivors to know who their ‘go-to’ medical provider is.” 

A randomized trial comparing survivorship care plans with standard oncologist discharge visits in patients with breast cancer found no differences in outcomes among the groups.

Jonathan S. Batchelor

Articles

Metformin May Decrease Diabetics' Breast Cancer Risk

Yoga Benefits Patients With Breast Cancer

Breast Cancer Survivors Vulnerable to Long-Term Work Loss

Survivorship Care Plans Do Not Improve Outcomes for Patients With Breast Cancer