Women with a history of infertility, and have undergone hormonal fertility treatment have denser breast tissue, which may increase their risk of developing breast cancer, according to a study published in the journal 

Researchers with the Karolinska Institutet in Sweden discovered this after conducting a 3-year study of 43,313 women, aged 40 to 69 as part of the KARolinska MAmmography (KARMA) project for risk prediction of breast cancer.

Of those women, 8963 reported fertility problems and 1576 had undergone controlled ovarian stimulation (COS) or a hormone treatment required for in vitro fertilization. Another 1429 had hormonal stimulation without COS, and 5958 had not received any hormonal fertility treatment.

COS is a hormone replacement therapy that increases estrogen and progesterone levels. It has been suspected of increasing a patient’s risk in developing breast cancer.

Breast density can also play a role in increased breast cancer risk. Previous studies have indicated that women who have extremely dense breasts are at least 4 to 6 times more likely to develop breast cancer than women with nondense, fatty tissue breasts.

Hormone replacement therapy, like COS, increases estrogen and progesterone levels and has been suspected to increase breast cancer risk. This is the first population-based study to investigate the effect of infertility and hormone stimulation on mammographic density which may be a useful marker for the effect of hormonal fertility treatment on breast cancer risk, especially in women below the age at which breast cancer is normally diagnosed (≥50 years).

The authors of the study stated that women with a history of infertility had a 1.53 cm higher absolute dense volume compared to noninfertile women. Among the group of infertile women, those who had gone through COS treatment had higher absolute dense volume compared with those who decided not to receive hormone therapy.

"The results from our study indicate that infertile women, especially those who undergo COS, might represent a group with an increased breast cancer risk,” Frida Lundberg, lead author of the study, said in a statement. “While we believe it is important to continue monitoring these women, the observed difference in breast tissue volume is relatively small and has only been linked to a modest increase in breast cancer risk in previous studies."

The researchers cautioned that due to the cross-sectional design of the study, which assessed history of infertility and breast density at the same time, no causal links between hormonal fertility treatment, infertility, and breast density could be established; however, the research team advised that continued monitoring of women undergoing COS is warranted.

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Lundberg FE, Johansson AL, Rodriguez-Wallberg K, et al. Association of infertility and fertility treatment with mammographic density in a large screening-based cohort of women: a cross-sectional study. 

Articles

Women with a history of infertility, and have undergone hormonal fertility treatment have denser breast tissue, which may increase their risk of developing breast cancer, according to a study published in the journal Breast Cancer Research.

Higher Breast Density Found in Women Who Received Hormonal Fertility Treatment 

Despite the proven effectiveness of a targeted drug for HER2-positive breast cancer, older women, especially black women, are still receiving it at low rates, according to a study conducted by researchers at the University of North Carolina at Chapel Hill (UNC) Lineberger Comprehensive Cancer Center.

The drug trastuzumab (Herceptin) is significantly increasing survival rates among HER2-positive patients. Specifically, a previous study found it increased survival rates by 37% when combined with chemotherapy compared with women who only received chemotherapy.

, examined 1362 women who were diagnosed with nonmetastatic HER2-positive breast cancer in 2010 and 2011. Participants were 66 years of age or older and insured through Medicare, which is how researchers were able to track data to investigate the rate of trastuzumab use among the study group.

Researchers found nearly half of all participants did not receive any trastuzumab, whereas 50% of white women and 40% of black women received some trastuzumab therapy. Additionally, 74% of white and 56% of black women with stage III of the disease received trastuzumab.

Black women were 25% less likely to receive treatment within the first year of diagnosis, even when researchers took into account other factors, such as poverty, tumor characteristics and comorbidity, which could have affected access to the treatment.

“In many ways, this is not surprising because we know that across many types of breast cancer therapy, black women are less likely to receive treatment for a clinically similar disease,” said the study’s first author Katherine Reeder-Hayes, MD, in a statement. 

“But one might hope that having a clear biological marker of eligibility for a treatment in this case—having overexpression of the HER2 receptor&mdash;would mitigate disparities because it would be an objective measure of who should receive the therapy.”

The research team noted, however, that the study consisted of several limitations, such as costs associated with the treatment option. Trastuzumab costs about $5000 per infusion, and while all study participants are insured under Medicare, their supplemental plans may vary.

Both the out-of-pocket costs that may incur as a result of the various plans as well as the length of time a patient receives the combination of trastuzumab and postsurgical chemotherapy are potential limiting factors to a patient’s access to this drug.

“It may not be possible to understand exactly which of these things is the driver of a disparity in a particular area,” Reeder-Hayes added. “But I think it’s important to recognize that the package of those factors together can serve as a warning sign of people who may be vulnerable to not getting the care that they need.”

Reeder-Hayes K, Peacock Hinton S, Meng K, Carey LA, Dusetzina SB. Disparities in use of human epidermal growth hormone receptor 2-targeted therapy for early-stage breast cancer [published online ahead of print April 11, 2016]. 

Disparities Found in HER2-Positive Breast Cancer Treatment in Older Women

Researchers have discovered that shorter, more intensive radiation treatment for patients in the early stages of prostate cancer can be performed without compromising cancer control

Currently, the standard regimen lasts 8 weeks to treat the cancer; however, the study, conducted by a team of researchers at the Duke Cancer Institute, shortened that therapy to 5.5 weeks.

The study involved 1100 men who had been diagnosed with early-stage prostate and compared two treatment regimens to determine whether the cure rates were similar.

Half of the men were randomly assigned to receive either the 5.5-week schedule that provided 28 hypofractionated radiotherapy (H-RT) treatments and the other half was assigned to the standard 8-week regimen control arm, which consisted of a total of 41 conventional radiotherapy (C-RT) treatments.

Researchers found that the 5-year disease free survival (DFS) rate was about 85.3% for men in the 8-week trial and 86.3% in the 5.5-week program. Additionally, overall survival (OS) was also no different between the groups, 93.2% and 92.5%, respectively.

“This study has implications for public policy,” said lead study author W. Robert Lee, a professor in the Department of Radiation Oncology at Duke, in a statement. “Because the shorter regimen has advantages such as greater patient convenience and lower costs, it’s important to establishing whether we can cure as many patients with the shorter regimen. Our study provides that information for the first time.”

One potential drawback of the H-RT regimen, however, is slightly higher side effects in patients. The study’s authors reported mild gastrointestinal and genitourinary toxicity was observed more frequently in patients getting the higher daily dose, shorter frequency radiation. However, no differenceswere observed in more severe side effects, which were occurred <5% with either regimen. The study also noted that data on patient experience with side effects are still be analyzed.

"An estimated 220,000 men are expected to be newly diagnosed with prostate cancer each year in the United States, and the majority will have early-stage disease at low risk for recurrence,” Lee noted. “These findings should help guide clinical decisions, and doctors should be comfortable recommending a shorter radiotherapy course as an alternative to the conventional schedule.”

Lee WR, Dignam JJ, Amin MB, et al. Randomized Phase III Noninferiority Study Comparing Two Radiotherapy Fractionation Schedules in Patients With Low-Risk Prostate Cancer [published online ahead of print April 4, 2016]. 

Researchers have discovered that shorter, more intensive radiation treatment for patients in the early stages of prostate cancer can be performed without compromising cancer control.

Shorter, Intensive Radiation Regimen Effective and Tolerable in Early-Stage Prostate Cancer 

A team of researchers at Brigham and Women’s Hospital (BWH) and the Dana-Farber Cancer Institute has discovered a set of 3 measurable risk factors that can help predict the magnitude of survival benefit offered by radiation therapy following breast-conserving surgery for ductal carcinoma in situ (DCIS).

“Radiation therapy after breast cancer surgery has become a widely accepted treatment option for patients undergoing breast-conserving therapy with DCIS. Our results provide information that can guide individual treatment options and better predict survival benefit from radiation therapy based on an individual’s case,” Mehra Golshan, MD, one of the study’s senior authors, explained in a statement.

Golshan, the Al-Tuwaijri Family Distinguished Chair of Surgical Oncology at Dana-Farber/Brigham and Women’s Cancer Center, and colleagues analyzed SEER data from 32,144 patients diagnosed with DCIS between the years 1988 and 2007.

Of this group, 20,329 patients were treated with radiation therapy following breast cancer surgery and the remaining 11,815 only underwent breast cancer surgery. At the conclusion of their retrospective, longitudinal, NIH-funded study, the research team found low cancer mortality rates at 10-years for both groups: 1.8% for patients who received radiation therapy and 2.1% for those who did not receive the therapy (HR, 0.73; 95% CI, 0.62-0.88). There were 304 breast cancer—specific deaths overall.

Each patient was assigned a validated prognostic score using a 0-6 scale based on 3 risk factors: nuclear grade, patient’s age, and tumor size. A higher nuclear grade, younger age, and/or larger DCIS received a higher score and vice versa.

They found that radiation therapy resulted in a significant survival benefit for patients with higher scores. Patients who scored a 4 or a 5 on the prognostic tests displayed a 70% reduction in breast cancer mortality if they were treated with radiation therapy after surgery. Patients with lower scores from both the radiation and surgery-only cohorts showed no significant difference in breast cancer mortality.

Although DCIS results in low cancer mortality overall, officials estimate that nearly 60,000 of Americans will be diagnosed with DCIS in 2016—a rate that has tripled in the past 3 decades.

“Using 3 factors that are routinely measured, we can predict whether there will be a survival benefit or no survival benefit for patients receiving radiation therapy,” lead author Yasuaki Sagara, MD, of the BWH Department of Surgery and Dana Farber/Brigham and Women's Cancer Center, said in a statement. “Our finding suggests, for the first time, that patients with more aggressive cancer who are at higher risk may actually live longer if they are treated with radiation therapy.”

Nonetheless, study investigators advised thorough counseling about the benefits and risks of radiation therapy for patients with DCIS who are seeking treatment options.

Sagara Y, Freedman RA, Vaz-Luis I, et al. Patient prognostic score and associations with survival improvement offered by radiotherapy after breast-conserving surgery for ductal carcinoma in situ: a population-based longitudinal cohort study. 

A team of researchers at Brigham and Women’s Hospital and the Dana-Farber Cancer Institute has discovered a set of 3 measurable risk factors that can help predict the magnitude of survival benefit offered by radiation therapy following breast-conserving surgery for ductal carcinoma in situ.

Three Prognostic Factors Found Predictive of Radiation Benefit for DCIS

Research has identified a correlation between a diet with a high glycemic index (GI) and an increased risk of developing lung cancer in non-Hispanic whites. The study found a nearly 50% higher risk in patients with the highest daily GI compared with those whose GI was lowest.

Accumulating evidence suggests that dietary factors may modulate lung cancer risk. The study, published in C

ancer Epidemiology, Biomarkers & Prevention

, is the largest to examine the relationship between GI and lung cancer and the first to examine this relationship in particular subgroups, including those who never smoked and those diagnosed with the squamous cell carcinoma (SCC) subtype of lung cancer.

GI is a measure of the quality of dietary carbohydrates, defined by how quickly blood sugar levels are raised following a meal. Glycemic load (GL), is a related measure of carbohydrate quantity.

“Diets high in glycemic index result in higher levels of blood glucose and insulin, which promote perturbations in the insulin-like growth factors (IGFs),” noted lead study author Stephanie Melkonian, a postdoctoral fellow at The University of Texas MD Anderson Cancer Center, in a statement. “Previous research suggests increased levels of IGFs are associated with increased lung cancer risk. However, the association between glycemic index and lung cancer risk was unclear.”

To further elucidate this relationship, the MD Anderson team surveyed nearly 1905 patients with newly diagnosed lung cancer and 2413 healthy individuals recruited from Kelsey-Seybold Clinics, a large physician group in the Houston area. Individuals reported their past dietary habits and health histories, including food frequency and portion size, through in-person interviews.

Participants were then divided into quintiles depending upon their answers. Those in the highest quintile of GI had a 49% increased risk of lung cancer versus those in the lowest quintile. Those in the highest quintile also had a 92% higher risk of developing SCC, but a less significant association was seen with developing adenocarcinoma.

Although tobacco use is the leading cause of lung cancer, among never-smokers in the highest quintile of GI, the researchers discovered that they were more than twice as likely to develop lung cancer as those in the lowest quintile. Among smokers, the risk was only elevated by 31% between the two groups.

GL was not associated with increased lung cancer risk for most patients, which the authors said suggests that it is the average quality, rather than quantity, of carbohydrates consumed which may impact lung cancer risk

The study also examined the impact of education, which is often related to socioeconomic status and has been linked with diet quality and smoking behaviors. Among participants with less than 12 years of education, those in the highest GI quintile had a 55% higher risk of developing lung cancer than those in the lowest quintile.

“Although smoking is a major, well-characterized risk factor for lung cancer, it does not account for all the variations in lung cancer risk,” said senior study author Xifeng Wu, MD, PhD, professor of epidemiology at MD Anderson, in a statement. “This study provides additional evidence that diet may independently and jointly with other risk factors impact lung cancer etiology.”

“Traditionally, glycemic index is only emphasized for diabetes prevention and management. However, if the results from this study are confirmed, healthcare providers should be made aware of the link between glycemic index and lung cancer, so they can communicate with their patients and the public about dietary changes for lung cancer prevention,” Wu continued.

Wu also noted that as a retrospective study, one limitation of the research is errors in participants’ recall and reporting of dietary intake; additionally, the study did not include information on whether participants had existing diabetes, hypertension, or heart disease.

The authors said that further research would be necessary to determine whether the association between GI and lung cancer carries over to other racial and ethnic groups.

Melkonian SC, Daniel CR, YeY, et al. Glycemic index, glycemic load, and lung cancer risk in non-Hispanic whites. 

Research has identified a correlation between a diet with a high glycemic index and an increased risk of developing lung cancer in non-Hispanic whites.

Study Finds Relationship Between Glycemic Index and Lung Cancer Risk

A study published by researchers at the Dana Farber-Cancer Institute recently discovered that financial status plays a large role in the level of symptom burden and quality of life for patients newly diagnosed with lung or colorectal cancer.

The aim of the study, published online in the 

, was to assess any relationship between a patient’s financial strain and the symptoms and quality of life (QOL) the patient reported upon diagnosis—earlier time points than the focus of previous research.

“Most of the studies looking at financial stress look at what cancer does to your finances after diagnosis,” Christopher Lathan, MD, MS, MPH, lead author of the study and a thoracic oncologist at Dana-Farber, said in a statement. “We were interested in looking at what happens when you have 

, defined in our study as little or no savings at the time of your diagnosis, and how that factor can impact quality of life.”

Study participants were drawn from patients in the Cancer Care Outcomes Research and Surveillance study. Patients were asked about their experienced QOL, symptom burden, and financial reserves, using validated assessments, such as the Brief Pain Inventory, the European Organization for Research and Treatment of Cancer Quality of Life Questionnaire C30, and  the EuroQoL-5 Dimension scale to gage responses for QOL.

Forty percent of patients with lung cancer and 33% of patients with colorectal cancer reported having limited financial reserves equivalent to 2 months or less. When compared with patients who had more than 12 months of financial reserves, these financially-strained patients with either lung or colorectal cancer reported significantly more pain, greater symptom burden and poorer quality of life.

The investigators also reported that as a patient’s financial resources decreased, a dose—response relationship emerged across all well-being measures, and this relationship persisted in outcomes reported by survivors after 1 year.

In follow-up interviews conducted 1 year after the baseline assessments, researchers found that patients across both tumor types who initially reported greater financial strain at diagnosis to have worse overall health, impairment in activity level, more pain, and more depression as compared with those with greater financial reserves.

“We found that patients who had financial distress at the time of diagnosis were more likely to have poorer outcomes in physical and mental quality of life measures, pain, and symptom burden. This effect persisted after adjusting for stage of disease, co-morbidity, income, age, and insurance,” Lathan added.

Study investigators hope that these findings will prompt healthcare professionals to evaluate patients for signs of financial distress at the time of initial diagnosis. Additionally, the research team urged clinicians to seek the appropriate resources and treatment options for patients who are already struggling financially before diagnosis.

Lathan C, Cronin A, Tucker-Seeley R, et al. Association of financial strain with symptom burden and quality of life for patients with lung or colorectal cancer [published online ahead of print February 29, 2016]

Symptom Burden Higher in Newly Diagnosed Patients Reporting Financial Strain

A majority of patients with cancer who undergo chemotherapy experience neuropathy as result of the treatment, and a new study conducted by researchers at The University of Texas MD Anderson Cancer Center suggests that neurofeedback can reduce the pain associated with the condition and improve quality of life.

“Chemotherapy-induced peripheral neuropathy (CIPN) is very common in patients with cancer, and there is currently only one medication approved to treat it,” noted lead study author Sarah Prinsloo, PhD, in a statement. Prinsloo is an assistant professor of palliative, rehabilitation, and integrative medicine at MD Anderson.

“I’m encouraged to see the significant improvements in patients’ quality of life after treatment. This treatment is customized to the individual, and is relatively inexpensive, noninvasive, and non-addictive.”

The study, which was presented at the recent annual meeting of the American Psychosomatic Society, enrolled 71 patients who scored higher than 3 on the National Cancer Institute’s neuropathy rating scale. The majority of participants were women with breast cancer (n = 52); 8 had a gynecologic cancer diagnosis, and the remaining 11 had other cancer types. The participants had an EEG and completed validated pain and symptom assessments, including the Brief Pain Inventory and the Pain Quality Assessment Scale, at baseline and after 10 weeks of treatment.

Patients were evenly randomized to either the neurofeedback arm or a waitlist control group. Neurofeedback is a method of brain training that induces neuroplasticity—the ability of the brain to form new connections and change existing ones.

For this study, researchers located the areas in the brain that contribute to the physical and emotional aspects of pain. With these identifiers, patients could modify their own brain activity through electroencephalogram (EEG) biofeedback, a device that tracks and records brainwave patterns through small metal discs with thin wires that are attached to the scalp and connect to a computer for results.

The group receiving neurofeedback engaged in 20 sessions of training where they played a computer game that rewarded them when they modified their brainwave activity in the affected area. Over time, they learned to modify the activity without an immediate reward from the game.

After the treatment, study participants had another EEG, and investigators noted that patients with CIPN exhibited specific and predictable EEG signatures that changed with the neurofeedback, which induced neuroplasticity to modulate brain activity and improve CIPN symptoms.

Participants also completed posttreatment symptom assessments to gauge changes in neuropathic pain. After controlling for participants’ baseline levels, pain was 3.5 with neurofeedback, versus 5.3 in the waitlist group; for numbness, levels were 2.9 and 5.6, respectively, and intensity (3.5 with the intervention versus 5.3 in the control arm). Overall, 73% of patients in the neurofeedback group experienced an improvement in pain and quality of life.

Prinsloo said that she found the findings to be statistically and clinically significant, and the results provide valuable information for better understanding neuropathic pain.

The researchers are planning a second study involving focused solely on patients with breast cancer who are experiencing neuropathic pain.

Prinsloo S, Novy D, Driver L, et al. Neurofeedback as treatment for chronic chemotherapy-induced peripheral neuropathy (CIPN). Presented at: American Psychosomatic Society Annual Meeting March 9-12, 2016; Denver, CO. Abstract 1567

Cate Douglass