Putting Immune Checkpoint Blockade to the Test in Breast Cancer


About 10 months ago, we asked: Is There a Future for Immunotherapy in Breast Cancer? Now, we can answer this question with a qualified “yes.” The data show why:

Triple-negative breast cancer (TNBC)

TNBC has long been considered to be more amenable to immune system-based treatments than other types of breast cancer because it is more immunogenic; that is, relatively high levels of immune cells accumulate within or adjacent to TNBC tumors. These immune cells could be triggered to attack tumors if properly activated. TNBC tumors are also likely to have a higher mutational burden (number of genetic mutations). This is one of the predictors of sensitivity to a type of treatment called immune checkpoint blockade.  Drugs known as checkpoint inhibitors block the proteins PD-1 or PD-L1. In cancer, PD-L1 proteins on tumor cells bind to PD-1 proteins on immune T cells and inhibit their tumor-killing activity. Immune checkpoint drugs disable this interaction and enable activation of T cells. These drugs are actively being explored in TNBC in clinical trials.

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T Cells That Recognize HER2 Teceptor May Prevent HER2+ Breast Cancer Recurrence

“Recurrence of HER2-positive breast cancer after treatment may be due to a specific and possibly cancer-induced weakness in the patient’s immune system—a weakness that in principle could be corrected with a HER2-targeted vaccine—according to a new study from the Perelman School of Medicine at the University of Pennsylvania. Results of the study show that T cells from patients whose breast cancer had recently recurred showed far weaker response to the HER2 receptor protein, compared to T cells from patients whose breast cancer had not recurred over a long period following treatment. The study, published in JAMA Oncology this week, suggests that patients with HER2-positive breast cancer—which accounts for roughly 20 percent of the 260,000 invasive breast cancers diagnosed in the US each year—might someday undergo immune status monitoring with blood tests before, during and after treatment, to allow physicians to gauge the risk of recurrence, and possibly to reduce that risk with therapies that boost anti-HER2 immunity.”


T-DM1 Improved Overall Survival for Heavily Pretreated Patients With HER2-positive Breast Cancer

“Among patients with HER2-positive, metastatic breast cancer that had progressed despite treatment with two or more forms of HER2-targeted therapy (trastuzumab [Herceptin] and lapatinib [Tykerb]), median overall survival was increased for those treated with trastuzumab emtansine (T-DM1 [Kadcyla]) compared with those who received treatment of physician’s choice, according to results from the phase III TH3RESA clinical trial presented at the 2015 San Antonio Breast Cancer Symposium, held Dec. 8–12.

“The HER2-targeted antibody-drug conjugate T-DM1 was approved by the U.S. Food and Drug Administration in February 2013 for treating patients with HER2-positive, metastatic breast cancer that had progressed after treatment with trastuzumab and a taxane.”


Video: Dr. Erika P. Hamilton on ONT-380 in HER2-Positive Breast Cancer Patients With Brain Metastases

Erika P. Hamilton, MD, associate director, Breast Cancer and Gynecologic Cancer Research Program, principal investigator, Sarah Cannon Research Institute, on ONT-380 for HER2-positive breast cancer and the treatment’s ability to cross the blood-brain barrier. Hamilton says the reason ONT-380’s ability to cross that barrier is important is because patients with HER2-positive breast cancer have a predilection to develop brain metastases.

She added that ONT-380 was proven to be effective when combined with capecitabine (Xeloda) and trastuzumab (Herceptin), though sometimes a combination of all three proved most useful. ONT-380 is a HER2-specific inhibitor and showed promising results when tested in patients with HER2-positive breast cancer who had previously received trastuzumab and T-DM1.

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Super Patient: Lyndsay Sung Catches Her Breast Cancer Just In Time


In 2013, Lyndsay Sung noticed something new on the edge of her right breast. “I felt something weird—an odd thickening along the rib,” she recalls. At the time, her son was only a year old, so she thought it might have been related to breastfeeding. But then she felt it again in September 2014. Lyndsay knew she was at risk for breast cancer because her grandmother had had it, and she also knew her breasts from years of self-exams. So she went to see her family doctor. Continue reading…


HER2-Enriched Molecular Subgroup Highly Sensitive to Breast Cancer Regimens

“The primary analysis of the phase III CALGB 40601 trial found that pathologic complete response (pCR) to dual HER2 blockade was not statistically higher than anti-HER2 monotherapy. However, there was a high level of intertumoral heterogeneity, and patients with the HER2-enriched subtype had a high pCR with both single and dual anti-HER2 therapy, according to data recently published in the Journal of Clinical Oncology.

“ ‘This trial paves the way for integrating molecular analyses into other trials in HER2-positive breast cancer, and may allow us to take a less-is-more approach for women who are selected to be highly sensitive to targeted treatments and to have a good prognosis,’ said lead study author Lisa Carey, MD, a UNC Lineberger member, the Richardson and Marilyn Jacobs Preyer Distinguished Professor in Breast Cancer Research at the University of North Carolina School of Medicine, and the physician-in-chief of the North Carolina Cancer Hospital, in a statement.”


Dual HER2 Blockade Fails to Improve Response Rate in HER2-Positive Breast Cancer

“Dual HER2 blockade with trastuzumab and lapatinib was no better than trastuzumab alone in producing pathologic complete responses (pCR) in metastatic HER2-positive breast cancer patients in the neoadjuvant setting, according to a new study. Those with hormone receptor–negative disease did see an improvement with the dual blockade.

“ ‘In randomized neoadjuvant trials, dual HER2 targeting generally results in higher pCR rates, but the magnitude of this effect has varied,’ wrote study authors led by Lisa A. Carey, MD, of the University of North Carolina at Chapel Hill. The new trial was a three-arm study of preoperative therapy in 305 patients with stage II/III HER2-positive breast cancer; 118 patients were randomized to paclitaxel along with trastuzumab and lapatinib, 120 to paclitaxel with trastuzumab alone, and another 67 to paclitaxel along with only lapatinib. That last trial arm was closed early. Results were published online ahead of print in the Journal of Clinical Oncology.”


No Benefit to Afatinib in HER2-Positive Breast Cancer With Brain Metastases

“The use of afatinib or afatinib plus vinorelbine during or after treatment with trastuzumab, lapatinib, or both failed to show a patient benefit in women with HER2-positive breast cancer with progressive brain metastases compared with investigator’s choice of treatment, according to the results of a phase II study published in Lancet Oncology.

“Afatinib, an oral inhibitor of the ErbB family of proteins, did benefit about one-third of patients assigned to the treatment, but had no better activity than investigator’s choice of therapy, which consisted mostly of trastuzumab or lapatinib plus chemotherapy.

“ ‘No objective responses were achieved in patients treated with afatinib alone, but around one-third of patients, including those treated with afatinib alone, did not have disease progression during the first 12 weeks,’ wrote researcher Javier Cortés, MD, of Vall d’Hebron Institute of Oncology in Barcelona, and colleagues. ‘No further development of afatinib for HER2-positive breast cancer is currently planned.’ “


To Type or to Print? Oncotype DX and Mamma/BluePrint Tests for Breast Cancer


Women diagnosed with localized breast cancer face difficult decisions with their doctors. What kind of neoadjuvant (before surgery) treatment to choose? Should chemotherapy follow surgery? Based on the subtype of breast cancer, should specific chemotherapy drugs be used? Continue reading…