New Drug Combination for Advanced Breast Cancer Delays Disease Progression

The gist: A new treatment that combines the drugs bortezomib and fulvestrant has shown promise in treating post-menopausal women with metastatic hormone receptor-positive breast cancer whose disease worsened after being treated with drugs called aromatase inhibitors. The combo treatment was tested in 118 patients in a clinical trial. It doubled the number of patients still alive after 12 months, and it lowered the chance of patients’ cancer worsening. Further studies will continue to measure the effectiveness of the treatment.

“A new combination of cancer drugs delayed disease progression for patients with hormone-receptor-positive metastatic breast cancer, according to a multi-center phase II trial. The findings of the randomized study (S6-03) were presented at the 2014 San Antonio Breast Cancer Symposium, held Dec. 6-9, by Kerin Adelson, M.D., assistant professor of medical oncology at Yale Cancer Center and chief quality officer at Smilow Cancer Hospital at Yale-New Haven.

“The trial enrolled 118 post-menopausal women with metastatic hormone-receptor-positive breast cancer whose cancer continued to progress after being treated with an aromatase inhibitor. The study, based on work done by Doris Germain of Mt. Sinai Hospital, found that the combination of the drugs bortezomib and fulvestrant—versus fulvestrant alone—doubled the rate of survival at 12 months and reduced the chance of cancer progression overall.

“Bortezomib, used most commonly in treating multiple myeloma, is a proteasome inhibitor that prevents cancer cells from clearing toxic material. Fulvestrant causes clumping of the estrogen-receptor protein. When bortezomib blocks the ability of the cell to clear these protein clumps, they grow larger and become toxic to the cancer cells. This, in turn, amplifies the effectiveness of fulvestrant, a drug commonly used in this subset of patients.

“The drug combination doubled the number of patients whose cancer had not progressed after one year from 14% to 28%, according to Adelson.”


Prognostic Role Found for miR-21 Expression in Triple-Negative Breast Cancer

The gist: New research shows that triple-negative breast cancer (TNBC) patients who have a particular molecule called miR-21 near their tumor, but not actually in the tumor cells, have worse clinical outcomes. This opens up the future possibility that doctors could check for miR-21 in order to better understand a patient’s disease and make treatment decisions.

” ‘Triple-negative’ breast cancer (TNBC) occurs in patients whose cells do not express receptors for estrogen, progesterone, and/or human epidermal growth factor receptor 2 (ER-/PR-/HER2-). Because of the absence of these predictive biomarkers, treatment assignment can be difficult. Now, researchers report that high levels of the microRNA miR-21 in the tumor microenvironment, but not in the tumor epithelia (cancer cells), are associated with worse clinical outcomes for patients with TNBC, thus identifying a possible TNBC prognostic biomarker, according to a study in The American Journal of Pathology.

“TNBC accounts for 15% to 20% of breast cancer cases, and patients have shorter recurrence-free survival (RFS) and breast cancer-specific survival (CSS) relative to other major subgroups. It is likely that different subtypes of TNBCs exist, and the heterogeneity may be responsible for a wide variation in response to treatment. ‘Predictive biomarkers for therapeutic response prediction and novel therapeutic targets that address distinct biological features of TNBC subgroups are needed for these patients,’ says Lorenzo F. Sempere, PhD, head of the Laboratory of microRNA Diagnostics and Therapeutics at Van Andel Research Institute in Grand Rapids, MI. ‘These findings add support to the growing importance of miRNA-based diagnostics.’ “


Sea Sponge Drug Could Boost Advanced Breast Cancer Survival by Five Extra Months

“The cancer drug eribulin, originally developed from sea sponges, could give women with advanced triple negative breast cancer an average of five extra months of life, according to research presented at the National Cancer Research Institute (NCRI) Cancer Conference in Liverpool.

“Researchers led by Professor Chris Twelves, based at the University of Leeds and Leeds Teaching Hospitals NHS Trust, looked at two major clinical trials of more than 1,800 women with breast cancer that had started to spread to other parts of the body. The phase III trials – the final stage of testing before deciding whether a drug can be prescribed to patients – compared the survival of women treated with eribulin* to those given standard treatment.

“The two studies showed an overall improvement in survival of more than two months for women treated with eribulin**. The most significant improvement was seen in women with the advanced triple negative form of breast cancer, where there are limited treatment options; these women’s survival improved by nearly five months. There was also a survival boost of more than two months for women with the HER2 negative form of breast cancer***.

“Cancer spreading to other organs – called metastasis – is responsible for around 90 per cent of all cancer deaths. And, when patients with breast cancer are diagnosed after the disease has started to spread, 10-year survival is around one in 10, compared to nearly nine in 10 for those diagnosed at the earliest stage.

“Study author, Professor Chris Twelves, said: ‘Our results show a substantial improvement in survival for women with metastatic triple negative breast cancer, and a more modest, but significant, benefit for those with HER2 negative breast cancers.’

“ ‘Eribulin has previously been offered to women who’ve already been through several lines of chemotherapy. But the European Union has recently approved eribulin for patients who have received less treatment for their breast cancer, which means we hope to give more patients another treatment option in the not-too-distant future.’ “


Subsidies Help Breast Cancer Patients Adhere to Hormone Therapy

“A federal prescription-subsidy program for low-income women on Medicare significantly improved their adherence to hormone therapy to prevent the recurrence of breast cancer after surgery.

” ‘Our findings suggest that out-of-pocket costs are a significant barrier’ to women complying with hormone therapy, said Dr. Alana Biggers, assistant professor of clinical medicine at the University of Illinois at Chicago College of Medicine, and lead investigator on the study. Programs that lower these costs can ‘improve adherence—and, hopefully, breast cancer outcomes—for low-income women,’ she said. Biggers presented the results of the study at an Oct. 14 press conference in advance of the American Society for Clinical Oncology Quality Care Symposium in Boston.

“Breast cancer is a leading cause of cancer-related deaths for women of all races, but survival rates differ by race and socioeconomic status, with African American women and women of low income having higher rates of death.”


Pfizer Announces FDA Acceptance of Palbociclib New Drug Application with Priority Review

The gist: In the U.S., a drug must be approved by the U.S. Food and Drug Administration (FDA) in order for it to be prescribed to patients with specific diseases. Particularly promising drugs might be granted Priority Review, meaning that the FDA agrees to work with the drug manufacturer to accelerate the approval process. The FDA recently granted priority review to a drug meant to treat certain breast cancer patients. The drug is called palbociclib. It is meant to be combined with another drug called letrozole as a treatment for “postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease.”  The FDA’s decision was based on promising results for the treatment in a clinical trial that tested it in volunteer patients. People who are interested in getting the treatment before it is approved can look into participating in Pfizer’s expanded access trial.

“Pfizer Inc. today announced the New Drug Application (NDA) for palbociclib has been accepted for filing and granted Priority Review by the United States Food and Drug Administration (FDA). This NDA requests FDA approval of palbociclib, in combination with letrozole, as a first-line treatment for postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease. The submission is based on the final results of PALOMA-1, a randomized, Phase 2 trial comparing palbociclib plus letrozole versus letrozole alone in this population of patients.

“The FDA’s Priority Review status accelerates the review time from 10 months to a goal of six months from the day of acceptance of filing and is given to drugs that may offer major advances in treatment or may provide a treatment where no adequate therapy exists. The Prescription Drug User Fee Act (PDUFA) goal date for a decision by the FDA is April 13, 2015.

“Palbociclib received Breakthrough Therapy designation from the FDA in April 2013, for the first-line systemic treatment of women with advanced or metastatic ER+, HER2- breast cancer.

“ ‘If approved as a first-line therapy in combination with letrozole, palbociclib will be an important new option for the thousands of women in the U.S. who are living with metastatic breast cancer,’ said Garry Nicholson, president, Pfizer Oncology. ‘We look forward to continuing to work closely with the FDA through the review process.’

“Pfizer recently announced the initiation of a multi-center, open-label expanded access program (EAP) in the United States for palbociclib. Through the program, palbociclib is available to post-menopausal women with hormone receptor-positive (HR+), HER2- advanced breast cancer who are eligible for letrozole therapy and for whom enrolling in other palbociclib clinical trials is not an option. Healthcare professionals and patients can learn more about the palbociclib EAP by visiting www.clinicaltrials.gov (trial number: NCT02142868).”


Lactation Linked to Reduced Estrogen Receptor-Negative, Triple-Negative Breast Cancer Risk

“Women who have had children (parous women) appear to have an increased risk of developing estrogen receptor-negative breast cancer, the subtype that carries a higher mortality rate and is more common in women of African ancestry. A similar relationship was found for triple-negative breast cancer. However, the association between childbearing and increased risk of estrogen receptor-negative and triple-negative breast cancer was largely confined to the women who had never breastfed. These findings, published in the Journal of the National Cancer Institute, suggest that low rates of breastfeeding in African American women may contribute to their higher incidence of the more aggressive and difficult-to-treat subtypes of breast cancer.

“Researchers from Boston University’s Slone Epidemiology Center (SEC) collaborated with the Roswell Park Cancer Institute of Buffalo, NY and the University of North Carolina Lineberger Cancer Center to form a consortium to study the determinants of breast cancer subtypes in African American women. They combined data on breast cancer cases and controls from four large studies, including the Boston University Black Women’s Health Study. The combined analyses included 3,698 African American women with breast cancer, including 1,252 with the estrogen receptor-negative subtype.

“They found that parous women had a 33 percent higher chance of developing estrogen receptor negative breast cancer than women who had never given birth. Women who had four or more births and had never breastfed any of their babies had a 68 percent higher chance of developing this type of cancer compared with women who had only one birth and had breastfed that baby. By contrast, parous women who had four or more births had a slightly decreased risk of estrogen receptor-positive breast cancer, regardless of whether or not they had breastfed.”


BRCA Mutation Incidence Comparable Between ER-Negative, ER-Low–Positive Breast Tumors

The gist: Researchers say that breast cancer patients younger than 60 who have ER-low-positive tumors should be “referred for genetic counseling and BRCA testing.” This is because a BRCA1 or BRCA2 mutation may affect treatment choices.

“The rate of deleterious BRCA1 or BRCA2 germline mutations detected in patients with ER-low–positive breast cancer is similar to that observed in patients with ER-negative breast cancer, according to study results presented at the Breast Cancer Symposium.

“The findings suggest the potential for underutilization of BRCA testing among appropriate patients, researchers wrote.

“ ‘In light of the life-saving interventions that may be offered to a patient once he or she has been identified to carry a deleterious BRCA mutation, we strongly recommend patients younger than age 60 with ER-low–positive tumors be referred for genetic counseling and consideration of BRCA testing,’ Rachel A. Sanford, MD, a fellow in cancer medicine at The University of Texas MD Anderson Cancer Center, said during a presentation.”


Breast Conserving Therapy Shows Survival Benefit Compared to Mastectomy in Early-Stage Patients

Editor’s note: Women with early-stage breast cancer have surgery to remove their tumors. They can choose between a mastectomy to remove the entire breast or a lumpectomy to remove the diseased part of the breast (breast conserving therapy, or BCT). Until now, it was thought that a mastectomy and BCT had similar results in terms of long-term survival for a patient. But a new study shows that BCT offers better survival for women who are PR-positive or ER-positive. Further studies are needed to figure out why. The researchers speculate it may have to do with the radiation treatment usually given just after BCT to keep the cancer from returning. Unfortunately, there appear to be socioeconomic barriers to receiving BCT instead of a mastectomy.

“When factoring in what is now known about breast cancer biology and heterogeneity, breast conserving therapy (BCT) may offer a greater survival benefit over mastectomy to women with early stage, hormone-receptor positive disease, according to research from The University of Texas MD Anderson Cancer Center.

“The study findings defy the conventional belief that the two treatment interventions offer equal survival, and show the need to revisit some standards of breast cancer practice in the modern era.

“The research was presented at the 2014 Breast Cancer Symposium by Catherine Parker, MD, formerly a fellow at MD Anderson, now at the University of Alabama Birmingham.”


Pfizer Submits NDA For Breast Cancer Drug Palbociclib Combined With Letrozole

Editor’s note: Before a new cancer treatment can be prescribed by doctors in the U.S., it must be approved by the U.S. Food and Drug Administration (FDA). Recently, the drug company Pfizer submitted an application to the FDA in the hopes that its new breast cancer treatment might be approved. The treatment combines two drugs called palbociclib and letrozole. It is specifically meant for treating advanced or metastatic breast cancer in post-menopausal women whose tumors have tested ER+ and HER2-. In addition, the women must not have already taken any other cancer treatments that travel through the bloodstream. The new treatment has performed well in a clinical trial with volunteer patients.

“Pharma giant Pfizer, Inc. ( PFE ) announced Monday that it submitted a New Drug Application or NDA, to the U.S. Food and Drug Administration or FDA, for palbociclib, in combination with letrozole, as first-line systemic treatment advanced or metastatic breast cancer in post-menopausal women.

” ‘Today’s submission marks an important milestone for Pfizer and palbociclib, and a potential advance for women with advanced breast cancer,’ said Garry Nicholson, President, Pfizer Oncology.

” is an investigational oral targeted agent that selectively inhibits cyclin-dependent kinases 4 and 6 to regain cell cycle control and block tumor cell proliferation.

“The NDA seeks approval for the treatment of postmenopausal women with estrogen receptor positive (ER+), human epidermal growth factor receptor 2 negative (HER2-) advanced breast cancer who have not received previous systemic treatment for their advanced disease.”