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…
“Ten-year overall survival for primary breast cancer patients treated with sentinel lymph node dissection (SLND) alone is similar to that seen in those treated with axillary lymph node dissection (ALND), according to a study published in the Sept. 12 issue of the Journal of the American Medical Association.
“Armando E. Giuliano, M.D., from the Cedars-Sinai Medical Center in Los Angeles, and colleagues compared the 10-year overall survival of patients with sentinel lymph node metastases treated with breast-conserving therapy and SLND alone without ALND (446 patients) versus women treated with ALND (445 patients). The women, with clinical T1 or T2 invasive breast cancer, all had planned lumpectomy, tangential whole-breast irradiation, and adjuvant systemic therapy.”
“In patients with metastatic triple negative breast cancer (TNBC), turning a nonimmunogenic (“cold”) tumor into an immunogenic (“hot”) tumor appears to be feasible, thereby improving sensitivity to immune therapy with nivolumab (Opdivo).
“In a phase II study of 50 patients with metastatic TNBC who received palliative chemotherapy, priming the immune system with low-dose chemotherapy for 2 weeks or radiation therapy before starting nivolumab resulted in a best objective response rate (ORR) of 24%, announced Marleen Kok, MD, at the 2017 ESMO Congress in Madrid.”
“Eli Lilly and Co.’s experimental breast cancer drug abemaciclib significantly cut the risk of disease progression in a late-stage trial, bolstering the drug’s potential to become a new source of growth for the Indianapolis pharma’s oncology business.
“Updated results from a late-stage study known as MONARCH 3, presented over the weekend at the European Society of Medical Oncology’s annual meeting, showed abemaciclib in combination with an aromatase inhibitor extended progression-free survival in previously untreated patients with metastatic breast cancer.
“Eli Lilly has previously said abemaciclib could be best in class, yet it’s not clear whether the data disclosed to date will be enough to outshine rival drugs already marketed by Pfizer Inc. and Novartis AG.”
“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.’ ”
“Even small tumours can be aggressive, according to a study in patients with early stage breast cancer that will be presented at the ESMO 2017 Congress in Madrid. Researchers found that nearly one in four small tumours were aggressive and patients benefited from chemotherapy. Aggressive tumours could be identified by a 70-gene signature.
” ‘Our results challenge the assumption that all small tumours are less serious and do not need adjuvant chemotherapy,’ said lead author Dr Konstantinos Tryfonidis, a researcher at the European Organisation for Research and Treatment of Cancer (EORTC), Brussels, Belgium.”
“Yesterday’s historic FDA approval of the first engineered T-cell treatment for cancer, Novartis’ Kymriah (tisagenlecleucel), was accompanied by inevitable questions about how the product would be priced. In the end, Novartis set the price at $475,000, which was lower than many analysts had predicted, considering the treatment is designed to cure some forms of acute lymphoblastic leukemia (ALL)—and in clinical trials it did just that for most patients.”
“Z-endoxifen, a potent derivative of the drug tamoxifen, could itself be a new treatment for the most common form of breast cancer in women with metastatic disease. This finding was reported from a clinical trial conducted by researchers at Mayo Clinic and the National Cancer Institute, and published in the Journal of Clinical Oncology.
“The final results of a first-in-human phase I study of Z-endoxifen in women with estrogen receptor positive metastatic breast cancer showed that the treatment was safe and resulted in tumor shrinkage in women whose tumors had progressed on standard anti-estrogen therapies, including tamoxifen.”