PracticeUpdate: Haematology & Oncology

SABCS 2016 23

Precision medicine in breast cancer: two new options from SABCS 2016

Dr Haffizulla: I’d like to highlight two unrelated studies that used different ways of more precisely targeting treatments in patients and to get your opinion on what we see for the future. The first study is the SAFIR 02 Breast Study. Targeted therapy was matched with specific genomic alterations in the maintenance setting. Can you comment on some of those results? Dr Pluard: The SAFIR trial looked at first- line metastatic breast cancer patients and profiled them genomically while they were receiving first-line therapy. At the time of completion of that therapy, they then were, if they had identified a targetable mutation, which they did in about two-thirds of the patients, they were randomised either to the targeted treatment of choice or conventional therapy. So we don’t have the results yet. They presented the preliminary data showing that you could, in 75% of the patients in a multicentre trial, actually be able to identify targets. So this was really a real-world example of how we can integrate genomics into our treatment program for metastatic breast cancer. Dr Haffizulla: In a different approach, the PALOMA study, researchers looked at the PAM50 HER2 subtype as a predictor of response to neoadjuvant lapatinib and trastuzumab. Can you comment on this study? cell-free DNA from liquid biopsies.” Clinically relevant results identified by next-generation sequencing in these tumours have been returned to clinicians and patients and are being used for clinical decisionmaking. Ultimately, the goal of this collaborative effort is to integrate functional and clinical findings into a unified “resistance atlas” for oestrogen receptor-positive metastatic breast cancer. This atlas should help inform treatment decisions for individual patients as well as propel the development of new combination treatment strategies for oestrogen recep- tor-positive metastatic breast cancer. A limitation of the study is that most samples were both metastatic and treatment-resistant. Therefore, potential “drivers” of metastasis were interwoven with that of drug resistance. The investigators are using several functional assays to help untangle metastasis-driving events from resistance-conferring events.

Dr Pluard: This is an interesting study in which [the investigators] took clinicallyHER2-positive patients and subjected them to PAM50 testing becausewe know that themolecular and clinical correlations are not 100%, and they looked at just non-chemotherapy, dual HER2 targeting therapy in the neoadjuvant setting. What they showed is that if you are HER2-enriched by PAM50, you had about a 40% pathologic complete response to non-chemotherapy regimens. So it potentially identifies a group of patients that may be able to avoid chemotherapy if they’re HER2-positive. Dr Haffizulla: Do you want to highlight any other precision approaches that may guide therapeutic options for patients? Dr Pluard: I think it’s very early, but what we’re also seeing in the triple-negative arena is that the PAM50 assay identifying intrinsic subtypes may be useful in sort of partitioning into separate groups that might have more specific targeted therapies, which is something that we’ve been lacking in the triple-negative population.

Timothy Pluard, MD, a medical oncologist and Medical Director at Saint Luke’s Cancer Specialists, Kansas City, Missouri, speaks with Dr Farzanna Haffizulla on the latest in precision medicine from presentations at SABCS 2016.

Farzanna Haffizulla, MD, FACP, FAMWA practices general internal medicine in Florida, within her own internal medicine concierge practice. She was previously

the National President of the American Medical Women’s Association (AMWA) 2014–2015.

that metastatic breast cancer samples harbour more frequent alterations in the ESR1, ERBB2, PIK3CA, PTEN, RB1, and AKT1 genes, among others. Transcriptomic sequencing helped identify several types of resistance likely to be clinically relevant. Dr Cohen remarked, “With increasing num- bers of patients from whom we were able to obtain and sequence the original primary tumour, we have been able to distinguish between pre-existing events (found in both primary and metastatic samples) and evo- lutionary, acquired events (found only in metastatic samples).” He continued, “Pre-existing events may highlight events that predispose to metasta- sis, supporting the idea that comprehensive characterization of primary tumours might help predict metastatic potential. Acquired events, on the other hand, may suggest nov- el therapeutic approaches to overcome or prevent resistance, and highlight the idea of periodic monitoring with technologies such as

For decades, molecular response to treatment has been applied in the clinic to accurately monitor effectiveness of treatment and guide treatment decisions in patients with leukaemia, but not in patients with breast cancer. >24

PracticeUpdate Editorial Team

VOL. 2 • NO. 1 • 2017