Improved Prognosis for Patients With Estrogen Receptor–Positive Breast Cancer With Large Reductions in Mammographic Density After Tamoxifen Initiation

“Improved prognosis for women with estrogen receptor–positive breast cancer who experience a large reduction in mammographic density following the initiation of tamoxifen treatment extends to premenopausal as well as postmenopausal women, researchers reported in the Journal of the National Cancer Institute. While a previous analysis linked decline in mammographic density following initiation of tamoxifen with improved survival in postmenopausal women, this more recent evaluation of change also showed improved survival in premenopausal women ‘for whom tamoxifen is the primary anti-endocrine therapy,’ Nyante et al wrote.

“ ‘Mammographic density reflects the fibroglandular composition of the breast, and women with the highest levels have approximately four-fold higher breast cancer risk compared with women with the lowest density,’ the investigators noted. ‘Emerging evidence,’ they added, ‘indicates that density reductions specifically among tamoxifen users may predict treatment effectiveness in adjuvant and chemopreventative settings, which could have value for planning long-term treatment.’ ”


New Positive Data Emerge on Palbociclib, a Drug Recently Approved for ER+ Breast Cancer

“Palbociclib, an investigational oral medication that works by blocking molecules responsible for cancer cell growth, is well tolerated and extends progression-free survival (PFS) in newly diagnosed, advanced breast cancer patients, including those whose disease has stopped responding to traditional endocrine treatments. Results of the phase II study, led by researchers in the Abramson Cancer Center and the Perelman School of Medicine at the University of Pennsylvania , were published this month in Clinical Cancer Research. Earlier phase I results by researchers at Penn Medicine contributed to the development of palbociclib, which was recently approved by the U.S. Food and Drug Administration (FDA) for metastatic breast cancer patients just beginning to undergo endocrine therapy.

” ‘The FDA approval has expanded treatments options for many metastatic breast cancer patients, but these new results are showing how effective the drug can also be for breast cancer patients who have already tried endocrine therapies and may be running out of options,’ said lead investigator Angela DeMichele, MD, MSCE , associate professor in the division of Hematology/Oncology and Epidemiology and co-leader of the Breast Cancer Research Program at the Abramson Cancer Center. ‘Combined with the promising results from other trials looking at the effectiveness of this drug, our results indicate that palbociclib can extend the duration of disease control and produce tumor shrinkage in patients with estrogen-receptor positive (ER+) breast cancer, without the debilitating side effects of chemotherapy.’ “


FDA Has Not Yet Planned Meeting to Evaluate Palbociclib for Postmenopausal Women with Advanced ER+ HER2- Breast Cancer

The gist: In October, the U.S. Food and Drug Administration (FDA) announced that it had granted Priority Review to new breast cancer drug palbociclib, meaning that it would speed its review process to get the drug to more patients sooner. However, as of January 2015, the FDA has not yet planned a meeting to evaluate the drug. The reason for the delay has not been announced. Palbociclib has shown promise for postmenopausal women with advanced, ER-positive, HER2-negative breast cancer. If it is approved by the FDA, doctors across the U.S. will be able to prescribe palbociclib to these patients.

“The U.S. Food and Drug Administration isn’t planning an advisory committee meeting at this time to evaluate Pfizer Inc.’s experimental breast-cancer treatment, despite the drug having received priority-review status in October, the company said Thursday.

“Pfizer didn’t provide reasons for the delay, but said it continues to talk with the FDA about the application for palbociclib, also known by the brand name Ibrance.

“An FDA spokesperson wasn’t immediately available to respond.

“The drug is one of many experimental therapies that targets certain proteins in the body known as CDKs. Cancer hijacks these proteins to help tumor cells grow. Recent studies suggest that stopping these proteins can help stall cancer.”


Adding Palbociclib to Letrozole Treatment Delays Cancer Worsening in Postmenopausal Women with Advanced ER+ HER2- Breast Cancer

The gist: Adding the drug palbociclib to letrozole treatment might help delay cancer getting worse in postmenopausal women with advanced, ER-positive, HER2-negative breast cancer. That was the conclusion of a recent clinical trial that tested the drug combo in volunteer patients. The trial specifically tested the palbociclib/letrozole combo as a “first-line” treatment, meaning the first drugs given to a patient to treat their advanced cancer.

“In the phase II PALOMA-1/TRIO-18 trial reported in The Lancet Oncology, Finn et al found that the addition of palbociclib to letrozole resulted in significant improvement in progression-free survival as first-line treatment for advanced disease in postmenopausal women with estrogen receptor–positive/HER2-negative breast cancer. Palbociclib is an oral small-molecule inhibitor of cyclin-dependent kinases 4 and 6.

“In the open-label study, patients were enrolled in two sequential cohorts, one including patients on the basis of estrogen receptor–positive/HER2-negaitve status alone (cohort 1) and another that required presence of amplification of cyclin D1 (CCND1), loss of p16 (INK4A or CDKN2A), or both (cohort 2). In both cohorts, patients were randomly assigned between December 2009 and May 2012 to receive continuous letrozole at 2.5 mg daily with or without palbociclib at 125 mg once daily for 3 weeks followed by 1 week off in 28-day cycles…

“The investigators concluded: ‘The addition of palbociclib to letrozole in this phase 2 study significantly improved progression-free survival in women with advanced oestrogen receptor-positive and HER2-negative breast cancer. A phase 3 trial is currently underway.’ “


Study Shows that Prosigna Test Influences Docs' Chemo Recommendations for Women with ER+, Node-Negative Breast Cancer

The gist: A recent study showed that a test called Prosigna affects whether oncologists recommend chemotherapy to women with estrogen receptor (ER)-positive, node-negative breast cancer.

“NanoString Technologies, Inc. (NASDAQ:NSTG), a provider of life science tools for translational research and molecular diagnostic products, today announced that the results of the first Prosigna® Assay decision impact study presented at the 37th Annual CTRC-AACR San Antonio Breast Cancer Symposium (SABCS) showed that the use of the test significantly changed oncologists’ treatment recommendations. Conducted in collaboration with Grupo Español de Investigación del Cáncer de Mama (GEICAM), a Spanish breast cancer research group, this prospective study of the Prosigna Assay and its impact on the treatment of women with Estrogen Receptor-Positive (ER+), HER2-negative, node-negative breast cancer showed that the use of the test informed the oncologists’ recommendation whether or not to treat with adjuvant chemotherapy in addition to adjuvant endocrine therapy.

“ ‘We are very pleased to see that in this study, Prosigna was used by oncologists to make more informed decisions regarding the administration of adjuvant chemotherapy for early-stage breast cancer patients,’ stated Brad Gray, President and Chief Executive Officer of NanoString. ‘Also, we were pleased to recapitulate the results of our earlier analytical validation study, which showed that Prosigna can be run at multiple sites and generate high-quality, consistent results…’ ”

“Overall, the investigators concluded that Prosigna can be reliably performed in hospital laboratories to provide useful information beyond standard clinicopathological variables that oncologists can use to inform adjuvant treatment recommendations in clinical practice, and that this study provides additional evidence that Prosigna has analytical validity and clinical utility in real-world settings.”


Adding Pictilisib to Anastrozole Treatment Might Improve Responses for Patients with Early-Stage, ER+, HER2-, Luminal B Breast Cancer

The gist: The drug pictilisib might improve response to treatment with the drug anastrozole for patients with early-stage, ER-positive, HER2-negative, luminal B breast cancer. In a clinical trial, patients who took pictilisib with anastrozole had better responses than patients who took anastrozole alone.

“The addition of pictilisib to anastrozole improved anti-proliferative response through the reduction of Ki67 in patients with early-stage breast cancer and particularly among those with luminal B tumors, according to study results presented at the San Antonio Breast Cancer Symposium…

“Schmid and colleagues evaluated data from 73 post-menopausal women with newly diagnosed breast cancer. All women had ER-positive, HER-2–negative disease. Fifty-three percent of the women had luminal A tumors, and 47% had luminal B tumors.

“Researchers randomly assigned patients 2:1 to the PI3K inhibitor pictilisib (GCD-0941, Genentech) plus 1 mg anastrozole (n=50) or anastrozole alone (n=23) for 2 weeks prior to surgery. The dose of pictilisib was reduced from 340 mg to 260 mg due to a concern for side effects demonstrated on other studies…

“ ‘The data presented show that the addition of the PI3 kinase inhibitor pictilisib significantly increases the anti-proliferative response of anastrozole in ER-positive breast cancer,’ Schmid said. ‘Subsequent analyses suggest increased benefit of pictilisib for patients with luminal B and highly proliferative tumors.’ ”


Weekly Paclitaxel or Docetaxel Every 3 Weeks Improves Survival in Breast Cancer

The gist: A different treatment schedule after surgery might increase survival and time without cancer worsening for women with axillary node-negative or high-risk node-negative breast cancer. A clinical trial found that these women might benefit from taking the drug paclitaxel once per week or docetaxel once every three weeks, instead of paclitaxel once every three weeks. The same trial found that women with triple negative breast cancer (TNBC) also benefit from weekly paclitaxel. But docetaxel once every three weeks showed better results for women with ER-positive, HER2–negative breast cancer.

“Women with axillary node-negative or high-risk node-negative breast cancer achieved prolonged DFS and marginally improved OS when they received adjuvant paclitaxel every week or docetaxel every 3 weeks compared with paclitaxel every 3 weeks, according to phase 3 study results presented at the San Antonio Breast Cancer Symposium.

“Further, weekly paclitaxel extended DFS and OS in women with triple-negative breast cancer, whereas docetaxel administered every 3 weeks improved DFS in women with ER-positive, HER-2–negative disease.

“Joseph A. Sparano, MD, professor of medicine and women’s health at Albert Einstein College of Medicine, and colleagues evaluated various regimens in 4,954 women with axillary node-positive or high-risk node-negative breast cancer. Previously released results, based on a median 5.3 years of follow-up, showed those who received adjuvant weekly paclitaxel (HR=0.73; P=.0006) or docetaxel every 3 weeks (HR=0.77; P=.02) demonstrated longer DFS than women who received paclitaxel every 3 weeks.

“The current analysis occurred after a median 12.1 years of follow-up. The numbers of DFS events (1639 vs. 1048) and deaths (1283 vs. 686) in the current analysis vs. the previous report were substantially higher.”


Promising Drug Staves Off Cancer Worsening in Hormone Receptor-Positive Breast Cancer Patients

The gist: A drug called palbociclib may increase the amount of time that passes without cancer worsening for patients with advanced, estrogen receptor (ER)-positive, HER2-negative breast cancer. In a clinical trial, some patients were treated with palbociclib along with letrozole, and some were treated with letrozole alone. Patients who took both drugs went for twice as long without their cancer worsening than patients who took only letrozole. Learn more about palbociclib in breast cancer.

“In a groundbreaking study that offers new hope for women with advanced breast cancer, researchers from UCLA’s Jonsson Comprehensive Cancer Center have published final clinical trial results that showed the amount of time patients were on treatment without their cancer worsening (called progression-free survival) was effectively doubled in women with advanced breast cancer who took the experimental drug palbociclib.

“An investigational drug discovered and being developed by Pfizer Inc., palbociclib targets a key family of proteins (CDK4/6) responsible for cell growth by preventing them from dividing. Results of the multi-year phase 2 study showed a significant increase in PFS for patients with advanced breast cancer that was estrogen receptor positive (ER+), HER2-negative (HER2-), who were given a combination of the standard anti-estrogen treatment, letrozole, and palbociclib compared to letrozole alone.

” ‘We’re essentially putting the brakes on cell proliferation and causing these tumor cells to stop growing,’ said Dr. Richard Finn, associate professor of medicine at UCLA and lead author of the study.

“The study was published online ahead of print in the journal The Lancet Oncology.”


SABCS 2014: PI3K Inhibition With Pictilisib in Hormone Receptor–Positive Breast Cancer Not Ready for Prime Time

The gist: Researchers are hoping a treatment approach called ‘PI3K inhibition’ might improve outcomes for people with hormone receptor-positive breast cancer. But it’s unclear whether the approach will be successful, and a recent attempt did not give stellar results. In a clinical trial, researchers gave patients the PI3K inhibitor drug pictilisib along with the drug fulvestrant (Faslodex). It did not significantly lengthen the amount of time patients went without their cancer worsening. But later analysis showed that it did stave off cancer getting worse in certain patients: women whose breast cancer is both estrogen receptor-positive (ER+) and progesterone receptor–positive (PR+). Further research is needed to see if any PI3K drugs are particularly effective. For more information, click through to the full article and see this other article from Cancer Network.

“Interest is high in studying the PI3K pathway in hormone receptor–positive breast cancer, but it is not clear which of the PI3K inhibitors under development—if any—will be a ‘home run.’

“Adding the pan-class I selective PI3K inhibitor pictilisib to fulvestrant (Faslodex) did not significantly improve progression-free survival in women with estrogen receptor–positive breast cancer, but in an exploratory analysis of the trial, progression-free survival was significantly extended in women with both estrogen receptor–positive and progesterone receptor–positive breast cancer. The findings were presented at the 2014 San Antonio Breast Cancer Symposium (Abstract S2-02).

“ ‘When we considered only women with breast cancer positive for both estrogen receptor and progesterone receptor, adding pictilisib resulted in a significant doubling of progression-free survival in an exploratory analysis. We plan to investigate whether the benefit of pictilisib for women with estrogen receptor-/progesterone receptor–positive breast cancer holds true in an additional cohort of patients within this study,’ stated lead author Ian Krop, MD, Director of Clinical Research for the Breast Oncology Program at the Dana-Farber Cancer Institute, Boston.”