Jason Harris

Obese patients being treated for breast or prostate cancer showed higher levels of mental and physical distress than nonobese patients, according to results from a retrospective study of more than 4,000 patients age 55 and older.

Investigators did not find the same correlation between obesity and distress in patients with colorectal cancer (CRC). Instead, those patients experienced “significant symptoms and distress” regardless of weight.

Lead study author Errol J. Philip, of the University of California, San Francisco, said the results do not suggest that obesity causes distress in patients with cancer. However, the findings showed a consistent association between excess weight and poorer psychosocial outcomes.

“In patients with breast cancer, obesity was associated with problems around sleep, fatigue, pain and physical functioning such as walking or climbing stairs,” he said in an interview. “We saw a similar pattern among the prostate cancer patients. They also reported high levels of fatigue as well as issues around sexual functioning.

“We can't make any causational arguments at this point, but we're able to identify a number of associations aligned with the broader literature that provide us with better insight into the experiences of patients as they move through treatment with and without excess weight.”

Results from previous studies in the general population have found an association between increasing body mass index (BMI) and greater pain, fatigue and sleep disorders. Furthermore, some reports have found that obese people are at higher risk for certain psychiatric illnesses, especially depression. Philip and his colleagues sought to determine if these observations held true in patients with cancer as well.

Investigators analyzed data from 4,159 patients who were treated at a large comprehensive cancer center in California from 2009 to 2017. Patients eligible for this study were 55 years or older and diagnosed with postmenopausal breast (52.2%), prostate (38.7%) or colon (9.1%) cancer.

Those with a body mass index (BMI) of 30 kg/m

 or more were classified as obese. Mean BMI was highest among patients with prostate cancer (28.6 kg/m

) compared with patients who had breast (28.1 kg/m

) cancer. However, more patients with breast disease (57.9%) were considered obese compared with those with prostate (53.9%) or colon (52.7%) cancer.

As a routine part of care, patients answered questions assessing their distress before starting treatment. They were asked to rank the levels to which they had experienced 33 problems on a five&#8208;point scale from one (not a problem) to five (very severe problem). The questions focused on five domains: physical, practical, functional, emotional and other.

Investigators observed higher distress scores in obese versus nonobese patients in breast cancer (4.6 versus 4.0) and prostate cancer (3.13 versus 2.52). Obese patients in both cohorts also reported more physical, practical, functional and emotional problems.

In contrast, nonobese patients with CRC reported higher distress scores than obese patients (4.12 vs 3.56). Moreover, investigators did not observe a significant difference in physical, practical, functional, emotional or other problem scores between obese and nonobese patients.

The CRC cohort was much smaller than the other groups and Philip suggested that it might have been too small to generate an accurate picture of weight-based distress in these patients.

“Both groups (of CRC patients), regardless of weight status, tended to report fairly high levels of distress. It's possible that the nature of the disease and the sorts of side effects and symptoms that they experience washed out any effect of weight that we could have seen,” he added. “Other studies that have examined the same relationships among CRC patients, ones that have larger numbers of individuals involved, did see that sort of pattern between excess weight and greater symptom burden or greater distress.”

Philip noted that it is impossible for investigators in this study to know how much distress obese patients might have been experiencing prior to diagnosis. Obese people routinely face bias and shaming, so it is possible that these results are capturing elevated stress levels among this population in general, rather than something specific to obese patients being treated for cancer.

“We know that within the general populace, with or without cancer, there is a lot of discrimination and stigma surrounding (obesity),” Philip said. “That's definitely an element that plays into it.”

The U.S. Preventive Services Task Force issued nutrition and exercise recommendations for patients and survivors in 2012. These guidelines say that patients should be as active as possible. Furthermore, survivors are at increased risk for secondary cancers and chronic diseases including cardiovascular disease, diabetes and osteoporosis, and exercise is crucial tool for prevention.

Philip added that published reports show excess weight is associated with poorer outcomes for patients with cancer. The “million-dollar question,” he said, is: How does obesity affect patients as they move through treatment and post-treatment when it comes to symptom burden and engaging in health-promoting behavior?

“We're asking patients to move and eat better, but if you're dealing with a lot of side effects or a lot of distress, that can be difficult,” he said. “If they are experiencing greater symptom burden and poorer outcomes, it is incumbent upon (the medical community) to provide greater support and work out ways to promote health and well-being across that treatment and survivorship period.”

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Obese patients being treated for breast or prostate cancer showed higher levels of mental and physical distress than nonobese patients with these diseases, but the pattern did not hold true in those with colorectal cancer, according to a study.
 

Obesity Linked With Higher Distress in Breast and Prostate Cancers

In May, the Pink Luminous Advocacy Project introduced the Breast Awareness app, the first multilingual, unisex breast self-examination application. Although the nonprofit Pink Luminous organization is tasked with supporting breast health in underprivileged communities, CEO Marilyn Dans maintains that the app is meant to encourage self-examinations across the population.

“In all the places we’ve gone and the women we’ve talked to, women feel uncomfortable with breast self-examination, so the app makes it easier,” she said in an interview with 

’s. “[The app] is trying make self-examination really simple, trying to educate and empower individuals to live an awareness lifestyle, to embrace the awareness lifestyle, to make it part of their routine.”

According to an analysis of the Surveillance, Epidemiology, and End Results database, the incidence of breast cancer with distant involvement at diagnosis increased by 2.07% annually in women aged 25 to 39 years from 1976 to 2009. Over the study period, the increased incidence was particularly acute among black (annual percentage change, 3.50%) and Latino women (annual percentage change, 2.67%).

Dans said that an increase in diagnoses among younger women, whose mammograms often are not covered by insurance, inspired Pink Luminous to develop an app to assist these women in particular and, more generally, anyone at risk for breast cancer. The idea was to create something to walk these men and women through a self-exam.

The Pink Luminous Advocacy Project supports and promotes breast cancer awareness in places where education and, specifically, medical education are limited. The organization’s ultimate goal is to “save lives at a global scale by offering educational tools focused on increasing breast health awareness.”

The app presents instructions for self-examination, similar to recommendations from the American Cancer Society, in both text and voice-over formats. It is currently available in English and Spanish and will download in the language set on the user’s device. Dans said a forthcoming update will include more languages.

Early detection is key to successful breast cancer treatment, and regular self-examination can help detect the disease early. The Breast Awareness app serves to educate users and help them become more familiar with their bodies. Dans says it gives individuals the tools to perform routine breast health examinations at home while teaching them how to detect possible abnormalities that require immediate action.

The app, available for Apple and Android, could benefit black and Latino women, who are often diagnosed with advanced disease and are more likely to die from breast cancer compared with white women, and women who face cultural barriers to screening. In a meta-analysis of 39 studies encompassing more than 5.8 million patients, black and Latino populations had lower odds of undergoing screening mammography compared with the white population.

Lead author Dr. Ahmed T. Ahmed said in an interview with 

 that early detection can reduce the risk for disease-specific death by 20%. He added that factors including socioeconomic status, insurance coverage, location, culture, language barriers and religion play a role in screening rates.

Muslim women, for example, are not routinely screened and treated for breast cancer because breast exams and mammograms are not widely accepted in that community, Ahmed said.

“The purpose is to be aware of what your normal breasts feel and look like, to detect any changes, and then to bring up those changes with your doctor,” said Dr. Giselle B. Ghurani, a gynecologist/oncologist with Mercy Hospital in Miami, Florida, and a member of the Pink Luminous advisory board. “The next step would be to raise concerns with a physician, usually a gynecologist.

The app also allows users to create a philanthropic channel and raise money for the Pink Luminous Advocacy Project. Those funds go to supporting the distribution of Pink Luminous Breast devices to women in need, the donation of sonogram machines to breast cancer clinics and the construction of health facilities in developing countries.

“I treat both healthy women and women who are at increased risk for breast and ovarian cancers, as well as women with (gynecologic) cancers. Early detection and disease prevention have always been a big passion of mine because I see how devastating the cancer diagnosis and treatment can be for the patient, the family, and the whole community.”

The Pink Luminous Advocacy Project has introduced the Breast Awareness app, the first multilingual, unisex breast self-examination application.

First Multilingual App for Breast Exam Aims to Improve Early Detection

Immunotherapy pioneers James P. Allison, Ph.D., and Tasuku Honjo, M.D., Ph.D., have won the 2018 Nobel Prize in Physiology or Medicine for their research that eventually led to the use of immune checkpoint

 inhibitors to treat cancer. The Nobel Assembly at Karolinska Institutet announced the award in a statement Monday.

“Cancer kills millions of people every year and is one of humanity’s greatest health challenges,” the committee said. “By stimulating the inherent ability of our immune system to attack tumor cells, this year’s Nobel Laureates have established an entirely new principle for cancer therapy.”

Allison, chair of Immunology and executive director of the Immunotherapy Platform at The University of Texas MD Anderson Cancer Center, is best known for his work in T-cell response mechanisms and his discovery that blocking the signaling of the immune checkpoint protein CTLA-4 improved antitumor immune responses. His research led to the development of Yervoy (ipilimumab), the first FDA-approved immune checkpoint inhibitor. The agency approved Yervoy the treatment of advanced melanoma in 2011.

Honjo, a professor in the Department of Immunology and Genomic Medicine at Japan’s Kyoto University Graduate School of Medicine, discovered PD-1 on the surface of immune cells in 1992 and later demonstrated that the protein inhibited immune response. His research eventually led to the development of Keytruda (pembrolizumab) and Opdivo (nivolumab), both of which were approved for the treatment of advanced melanoma in 2014.

Clinical trials have shown that PD-1 blockade has resulted in positive outcomes for patients with lung cancer, renal cancer and lymphoma.

Allison said in a press conference that he first learned the Nobel Committee’s decision from a phone call from his son at 5:30 a.m. He was still in shock hours later.

“It still hasn’t completely dawned on me,” he said. “As a basic scientist, to have my work impact people is one of the best things I can think about. It’s every scientist’s dream to do fundamental work that’s important, but then to have it translate into helping people is all that much better. Then to have that work recognized by the Nobel Committee is going to bring attention to the issues, the importance of basic science, and that there is hope for cancer patients.”

In 2015, Allison won the Lasker-DeBakey Clinical Medical Research Award honoring investigators whose contributions have improved clinical treatment. That same year, he won ASCO’s Science of Oncology Award and the Pezcoller Foundation—AACR International Award for Cancer Research. He was also recognized as a 2014 Giants of Cancer Care

 in Scientific Advances. Honjo and Allison were joint recipients of the first Tang Prize for Biopharmaceutical Science in 2014.

Honjo won the Smalley Award from the Society for Immunotherapy of Cancer in 2015 and the Keio Medical Science Prize in 2016. That award from Keio University recognizes researchers who have made an outstanding contribution to medicine or the life sciences. Honjo is the eighth Keio Prize winner to later become a Nobel Laureate.

Final results from the phase 3 KEYNOTE-006 trial of patients with unresectable stage 3/4 advanced melanoma showed that frontline Keytruda continues to demonstrate long-term efficacy. At two years, patients assigned to Keytruda had an overall survival (OS) of 55 percent versus 43 percent for those assigned to Yervoy.

The FDA approved Keytruda in this setting in 2015 based on results from this trial.

In the study that led to the approval of Yervoy for patients with unresectable or metastatic melanoma following at least one prior systemic treatment, OS was longer with Yervoy alone compared with the experimental tumor vaccine gp100. Patients treated with Yervoy alone had a median OS of 10 months compared with six months for those treated with gp100.

Follow-up studies have since shown that 20 percent of patients survive at least three years posttreatment, with many living for 10 years and beyond. Subsequent research has led to agents targeting additional immune checkpoints, often PD-1 and PD-L1, to treat a range of cancers including head and neck, gastric kidney, bladder, gastric, liver, colorectal, and cervical cancers and Hodgkin lymphoma.

Allison said that one patient with metastatic melanoma from the phase 1 trial is still alive almost 19 years later following a single dose of Yervoy. He said that clinicians and investigators have come to accept immunotherapy as the fourth pillar of cancer care along with radiation, surgery and chemotherapy.

“What we’re looking forward to is combinations, not just of multiple checkpoints but of checkpoints with radiation, checkpoints with chemotherapy, [and] checkpoints with genetically targeted small molecule drugs,” he said. “Immunotherapy is going to be part, it’s not going to replace the others, but it’s going to be part of the therapy that essentially all cancer patients are going to be receiving in five years.”

This article originally appeared on OncLive’s web site, title “

Allison, Honjo Win Nobel Prize for Research on Immune Checkpoints

Immunotherapy pioneers James P. Allison, Ph.D., and Tasuku Honjo, M.D., Ph.D., have won the 2018 Nobel Prize in Physiology or Medicine for their research that eventually led to the use of immune checkpoint inhibitors to treat cancer.

Immunotherapy Researchers Win Nobel Prize

Alan D’Andrea, M.D., co-leader of the Stand Up to Cancer Dream Team on Ovarian Cancer, wants to know why diagnosing ovarian cancer can’t be more like diagnosing a sore throat.

Presenting an update on the Dream Team’s work during the 2018 Ovarian Cancer National Conference, sponsored by the Ovarian Cancer Research Fund Alliance, he said that when a person gets a sore throat, he or she goes to the doctor’s office and gets a throat swab. That swab gets cultured in the lab and, a few days later, the doctor’s office calls with a diagnosis and a treatment recommendation.

“The question has always been: In cancer, why can't we do that with tumors? Why can't we take a swab or a biopsy of a solid tumor, plate it out in a dish, grow it out for two or three or four days, and then test our drugs on these growing tumor cells?” D’Andrea, director of the Susan F. Smith Center for Women’s Cancers at Dana-Farber Cancer Institute in Boston, said during his July 14 talk in Washington, D.C. “Is it sensitive to a PARP (protein) inhibitor? Is it sensitive to a carboplatin (chemotherapy)? Is it sensitive to an immunotherapy? Is it sensitive to a combination of those drugs? Why can't we do testing directly on the tumors themselves?"

The breakthrough, he said, is that investigators are learning how to take a tumor biopsy from a newly diagnosed or relapsed patient, chop it up into a single-cell suspension and grow small tumors called organoids within a week. D’Andrea believes that direct testing on these organoids will help physicians find the best combination of drugs to kill tumor cells "right now." For a short time, these organoids look and behave exactly like the larger tumor.

"Now, you can do a direct drug testing on these organoids just like you do with a throat culture for penicillin testing,” he said. “You can test these little organoids for their sensitivity to a drug.”

Chemotherapy sensitivity testing on cell lines has existed for a couple of decades, but testing on organoids is a newer method with the potential for higher accuracy.

Investigators collected tumor cells from biopsies of 12 consecutive patients treated for ovarian cancer at Dana-Farber and grew organoids of their cancers. Three women’s cancers expressed BRCA gene mutations and one expressed a RAD51C mutation, making this group a reasonably good representation of ovarian tumors in the general population, according to D'Andrea.

He highlighted results from the analysis of one patient's organoids. She was found to have  the BRCA1 gene mutation, suggesting that her cancer should respond well to a PARP inhibitor such as Lyparza (olaparib), but her organoids showed that her cancer was resistant to the drug.

“This woman's ovarian tumor . . . in the clinic was not responding to the PARP inhibitor,” D’Andrea said. “Her clinical response, in the clinic, was matching the sensitivity and resistance of these organoid cultures in the laboratory.

“This is the kind of information we can give to the clinician — quickly. We can say, 'You know, these organoids are very resistant to the PARP inhibitor; maybe we should switch to a different drug, and do it early.'

“We can't say that yet, because this hasn't been clinically certified the way that penicillin testing for a sore throat is. But we're getting there.”

D’Andrea said this method of direct testing will be particularly effective and important for predicting drug resistance. He highlighted another patient, the one whose tumor expressed the RAD51C mutation, noting that her organoids were resistant to every drug investigators tried. In line with that finding, her disease was not responding to treatment in the clinic.

“There really did seem to be a perfect match between the resistance of the drugs in the test tube and the resistance of the tumor in the patient,” he said. “We found this out within two weeks of the time of the biopsy. So, rather than put this patient through four cycles of chemotherapy that's not going to work, why don't we get that information back to the doctor sooner so we can switch to a combination of drugs, or maybe try a clinical trial of a new immunotherapy agent?”

D’Andrea noted that direct testing is in the earliest stages of evaluation. Nonetheless, he has high hopes for the future of direct testing.

“It’s a kind of precision medicine, and I think over time, this is going to grow in utility,” he said.

Stand Up To Cancer, a division of the nonprofit Entertainment Industry Foundation, raises money for grants it gives to 22 Dream Teams of scientists from various hospitals and institutions who collaborate to develop new treatments. SU2C is 10 years old, and in that time, it has accepted more than $480 million in pledges to support its cancer research, and the work of its scientists has contributed to the Food and Drug Administration’s approval of five new cancer treatments.

Investigators are learning how to take a tumor biopsy from a patient, grow small tumors called organoids in the lab, and test cancer treatments on them to see which work best.

Jason Harris | Contributors

Obesity Linked With Higher Distress in Breast and Prostate Cancers

First Multilingual App for Breast Exam Aims to Improve Early Detection

Immunotherapy Researchers Win Nobel Prize

Dream Team Evaluates Direct Testing of Tumors

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