“As a medical oncologist and investigator, Rinath M. Jeselsohn, MD, focuses on the detection and clinical implications of ESR1 mutations in estrogen receptor–positive breast cancer. She is a member of the research team in the lab of Myles A. Brown, MD, at Dana-Farber Cancer Institute in Boston, Massachusetts, where investigators are seeking to elucidate the factors underlying the mechanisms of hormone responsiveness, particularly steroid hormone receptors, in human cancers.
“Jeselsohn, who has led numerous studies into ESR1 mutations, discussed the field in an interview with OncologyLive®.”
“Mutations in HER2 were found to confer resistance to hormone therapy in some estrogen receptor (ER)-positive metastatic breast cancer cases, and resistance could be reversed by dual treatment with the hormone therapy fulvestrant (Faslodex) and the HER2 kinase inhibitor neratinib (Nerlynx), according to data presented during a media preview for the 2018 American Association for Cancer Research (AACR) Annual Meeting, to be held April 14–18 in Chicago.”
“Endocrine therapy can achieve tumor reduction for patients with ER-positive breast cancer, possibly avoiding the need for chemotherapy or even surgery in some patients; however, deciding how long to continue this therapy can be tricky, said Hyman B. Muss, MD, who presented at the 2018 Miami Breast Cancer Conference.
” ‘It can improve the probability of breast preservation for women who would appropriately fit in [related] studies and don’t have very high-grade or aggressive tumors,’ said Muss, of the Lineberger Comprehensive Cancer Center, University of North Carolina, and a 2017 Giants of Cancer Care® winner. ‘The optimal duration is 3 to 6 months. I think it’s [also] worth considering this in postmenopausal women with larger tumors.’ ”
“A combined approach targeting estrogen receptor (ER), HER2, and RB1 yielded promising results in terms of Ki-67 expression in an exploratory study of women with HER2-positive, ER-positive breast cancer.
” ‘HER2-positive, ER-positive tumors have molecular features distinct from those of HER2-positive, ER-negative cancers, suggesting that the two types of tumors should be treated with differently tailored approaches,’ wrote study authors led by Luca Gianni, MD, of San Raffaele Scientific Institute in Milan. Previous work has suggested that a combined approach targeting HER2, ER, and RB1 may improve outcomes.”
“In women with estrogen receptor-positive, hormone-refractory metastatic breast cancer, oral Z-endoxifen hydrochloride, the potent metabolite of tamoxifen, provided substantial drug exposure regardless of CYP2D6 genotype, acceptable toxicity, and promising antitumor activity, researchers reported.
“Results from a phase I study in 38 patients with metastatic breast cancer demonstrated a clinical benefit rate (stable disease ≥ 6 months) of 26.3%. including a partial response by RECIST criteria in three patients who experienced progression during prior tamoxifen therapy, according to Matthew P. Goetz, MD, of the Mayo Clinic in Rochester, Minnesota, and colleagues.”
“As research of early-stage estrogen receptor (ER)-positive breast cancer continues, experts are relying more on extended adjuvant hormonal therapy with aromatase inhibitors, but are concerned about patient quality of life (QoL) with such treatment.
” ‘My passion is to really try to figure out how to make the side effects of these therapies more tolerable and how to help women be able to actually have reasonably good and normal QoL while they’re taking these therapies, so that we can increase compliance,’ said Michelle E. Melisko, MD.”
“The FDA granted fast track designation to elacestrant for the treatment of ER-positive, HER-2-negative advanced or metastatic breast cancer, according to the drug’s manufacturer.
“Elacestrant (RAD1901, Radius Health) an investigational oral selective ER downregulator/degrader is under investigation as a nonsteroidal treatment for hormone-driven or hormone-resistant breast cancer.”
Non-metastatic breast cancers are most often treated with surgery, but if the tumors are fairly large, or involve nearby lymph nodes, neoadjuvant (pre-operative) treatments with chemotherapy (NAC) are done first. NAC often reduces the tumor size and kills cancer cells in lymph nodes, if present, prior to surgery, improving the outcome. The best possible result of neoadjuvant treatment is pCR (pathologic compete response), when the tumor is no longer visible in imaging studies. Here, I review the new directions in which neoadjuvant treatments are evolving.
Today, treatments for metastatic breast cancers are tailored for specific subtypes. Starting with the introduction of the drug trastuzumab (Herceptin) for HER2-positive cancers, new, more specific treatment options were eventually developed and approved for other types as well. Estrogen deprivation endocrine therapies, lately prescribed in combination with CDK4/6 inhibitors, are used in estrogen receptor (ER)-positive cancers. Triple negative cancers (TNBC) are still treated mostly with chemotherapy, but immune checkpoint drugs and PARP inhibitors are explored in clinical trials, with some successes reported.
However, neoadjuvant treatments (except for HER2+ cancers) remain largely limited to chemotherapy regimens. This is starting to change now, with new approaches tailored to the cancer type being investigated in clinical trials.
In this regard, it is important to mention the I-SPY2 trial, NCT01042379, which started in 2010 and is for women with stage II-III breast cancer. It offers about a dozen drugs that are chosen based on particular features of the newly diagnosed cancers. This trial has a unique design and has produced some important results. Additional treatments and trials for various types of breast cancer are discussed below. Continue reading…
“Adding taselisib to letrozole before surgery significantly improved outcomes for patients with early breast cancer that was both estrogen receptor positive and HER2-negative (ER+/HER2-) according to results of the LORELEI trial, presented at the ESMO 2017 Congress in Madrid.
” ‘We were able to detect a reduction in tumor size after only 16 weeks of treatment, compared to patients who received letrozole plus placebo,’ said study investigator Dr. Cristina Saura, from Vall d’Hebron University Hospital in Barcelona, Spain. ‘Any decrease in tumor measurements is something positive for patients because this means the drug has had activity against their tumor in a short period of time.’ ”