Last year, we covered the five biggest advancements in breast cancer. As the piece proved so popular, this year we are once again bringing you the top breast cancer research and clinical highlights from 2018. We’d also love to hear your thoughts; let us know in the comments section below if you agree with our selection, or if you think a different research highlight should have made it into our top 5 list!
Olaparib for BRCA breast cancer
At the start of 2018, the US FDA made one of its most poignant approvals for breast cancer. It expanded the label for AstraZeneca’s (Cambridge, UK) oral PARP inhibitor Lynparza® (olaparib) to include the treatment of patients with metastatic breast cancer whose disease is associated with a BRCA gene mutation. Olaparib is also the first drug in its class (PARP inhibitor) approved to treat breast cancer.
The approval was based on the highly promising results published from the Phase III OLYMPIAD trial, which demonstrated that olaparib provided a significant benefit over standard therapy, reduced the chance of progression of advanced BRCA-related breast cancer by 42% and delayed progression by 2.8 months. You can access the full news story here.
We can’t cover breast cancer advancements without mentioning the hottest talk to come out of this year’s ASCO (American Society of Clinical Oncology, 1–5 June 2018, IL, USA) meeting – TAILORx. The practice-changing trial demonstrated that most women with a specific early stage breast cancer and midrange score on the Oncotype DX® test do not need chemotherapy after surgery. The findings will spare thousands of women from the harmful effects of chemotherapy.
We covered the news of the trial and whilst at ASCO had the opportunity to speak with Andrew Paramore from Genomic Health (CA, USA). To discover insider details of the trial and what is next for TAILORx, listen or read the full interview here.
Personalized immunotherapy leads to complete response in metastatic breast cancer patient
While ASCO was wrapping up, a case report created a storm of interest in the oncology community. The case came as part of an ongoing Phase II clinical trial (NCT01174121) investigating immunotherapy, using tumor-infiltrating lymphocytes (TILs), for patients with metastatic breast cancer.
The patient, a 49 year old woman with ER-positive, HER2-negative metastatic breast cancer that was refractory to multiple lines of chemotherapy and hormone treatments, was enrolled into the trial.
The patient had DNA and RNA from her tumors and normal tissue sequenced, identifying 62 unique mutations in her tumor cells. The researchers tested different TILs from the patient to find those that recognized one or more of these mutated proteins. TILs recognized four of the mutant proteins, and the TILs then were expanded and infused back into the patient. She was also administered the checkpoint inhibitor pembrolizumab to prevent the possible inactivation of the infused T cells by factors in the tumor microenvironment.
After the treatment, the patient’s cancer completely regressed, even after follow-up at 22 months. Read the full news story here.
Treasure troves of breast cancer genes discovered
As with immunotherapy, genetics has proved a fruitful area of research in 2018.
Earlier in the year, genome-wide association studies identified 110 genes linked to an increased risk of breast cancer. This study, which is the most comprehensive study ever to unpick the genetics of the disease, utilized a technique termed Capture Hi-C to study interactions between different regions of the genome. Read the full story:
Later on in the year we saw a great progress in the field of triple-negative breast cancer when researchers uncovered, for the first time, which genes are associated with high lifetime risks of triple-negative breast cancer.
By performing genetic testing using multigene panel testing in 10,901 patients diagnosed with triple-negative breast cancer from two studies, the investigation revealed that alterations in BARD1, BRCA1, BRCA2, PALB2 and RAD51D genes were associated with high risk for triple-negative breast cancer and greater than 20% lifetime risk for overall breast cancer among Caucasians. A similar trend was observed among African Americans. Read the full news story.
Another growing area of interest is circulating tumor cells and plasma DNA as tumor markers. They can reveal the telltale patterns of secondary variants in cancer-cell genomes, which could enable us to help identify patients who are destined to recur, therefore providing objective reasons for prescribing more intensive systemic therapies based on their “genome scar”. Read more on this concept in a paper in the New England Journal of Medicine.
Improvements in selection of patients for nipple sparing mastectomy
The panel consisted of 44 breast surgeons from 14 countries, across four continents, with a background in gynecology, general or reconstructive surgery and a practice dedicated to breast cancer, as well as a patient advocate.
Consensus recommendations were reached in 35, majority recommendations in 24 and no recommendations in the remaining 12 questions. The panel acknowledged the need for standardization of various aspects of NSM and immediate reconstruction. It endorsed several oncological contraindications to the preservation of the skin and nipple. Furthermore, it recommended inclusion of patients in prospective registries and routine assessment of patient-reported outcomes. Considerable heterogeneity in breast reconstruction practice became obvious during the conference.
Unlike NSCLC, melanoma and urothelial cancer, immunotherapy has yet to make a great impact in the field of breast cancer. Therefore, over the coming years there will be a great focus on improving these outcomes. Several FDA-approved agents are being tested in patients with breast cancer, including the PD-1 inhibitors pembrolizumab and nivolumab, and the PD-L1 inhibitors atezolizumab, avelumab and durvalumab. Long-term follow-up data will soon become available, which will help guide this area of research.
Additionally, increasing the number of patients who respond to immune checkpoint blockade is a major focus now, and the approach is to evaluate different strategies, including combinations of immune checkpoint inhibitors with chemotherapy, targeted therapy, other immunotherapy agents or radiation. The role of partnering immunotherapy and chemotherapy will be defined more by the results of several large Phase III randomized studies in the neoadjuvant setting. More information can be found here.
In order to predict the response to immune checkpoint blockade we need to also focus on identifying biomarkers. For example, it is likely that a combination panel of markers is needed to define appropriate patient selection for treatment with PD-1/PD-L1 blockade.
Across the cancer spectrum there is an effort to put personalized medicine into practice – achieving this will require the successful roll-out of genetic profiling, utilizing biomarkers and adopting technology that allows for assessing cancer risk among the population. We look forward to seeing how the breast cancer landscape evolves over the next year.