Five Questions With: Dr. Stephanie L. Graff

Dr. Stephanie L. Graff, director of breast oncology at Lifespan Cancer Institute, was named Woman Disruptor of the Year during the 2022 American Society of Clinical Oncology conference in June.

The honor, presented by Healio, a medical industry information website, is a highlight for Graff as she prepares to lead the next phases of the Destiny Breast clinical trials at Lifespan Corp. In initial trials, the Destiny Breast studies yielded promising results, dramatically increasing survival odds for some breast cancer patients. 

PBN: What is the significance of the Healio Disruptive Innovator Woman Disruptor of the Year award you received?

GRAFF: The award, which was given in partnership with City of Hope, goes to a woman who has emerged as a leader in the field and an example to younger women. I have been honored, through numerous leadership roles, as a champion for women in oncology. The opportunity to lead by example and mentor others in the field has been one of the most rewarding parts of my career.

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PBN: What are the Destiny Breast trials and how promising are they?

GRAFF: The Destiny breast trials are the full portfolio of trials using trastuzumab deruxtecan (Enhertu). The drug is an antibody-drug conjugate, which means “smart chemo” that goes specifically to a target (antibody) and delivers the chemotherapy (drug). The target in the case of Enhertu is Her2, the human epidermal growth factor receptor, which is a protein found in cells that determines their growth and survival.

Historically, we have thought of Her2 in the binary – Her2 positive or Her2 negative – with Her2 positive cells growing more quickly and Her2 negative cells growing more slowly. In truth, however, Her2 is gray-scale and expressed across a range on a scoring system from 0-3.

Enhertu was first tested in traditionally Her2 positive metastatic breast cancer where it dramatically improved survival. At the American Society of Clinical Oncology Annual Meeting in Chicago in June, the results of the drug in metastatic “Her2 low” breast cancer (Her2 1 or 2, the middle of that gray scale) showed it also improves survival significantly in this whole new disease definition, as well.

PBN: Will the trials be at Lifespan?

GRAFF: The Lifespan breast cancer team will be opening the next round of Destiny Breast trials looking at using the drug in earlier lines of treatment and in combination with traditional chemotherapy to see if we can both improve outcomes more and use it in combination safely. The overall goals of these studies will then be to see if we can move Enhertu to curative breast cancer treatment.

We also have three trials with a new antibody drug conjugate using the same chemotherapy (deruxtecan) but a different target (antibody).

PBN: What made you decide to move to Rhode Island in 2021 and join the Lifespan Cancer Institute?

GRAFF: I was drawn to the momentum and excitement happening at Lifespan and Brown [University]. Our goal is to move toward National Cancer Institute designation, which is the highest standard in the world for interdisciplinary care and state-of-the-art research.

I am thrilled to help Rhode Island establish ways to pair the right clinical trials, the right medicines and the right innovations for the patients we are honored to care for, and to be part of the effort to attain NCI designation.

PBN: What interested you in specializing in breast cancer?

GRAFF: The people! In medical school, I loved the science of oncology – the pathophysiology and the pharmacology. But when I got to clinical rotations, it was the deep human connection, the longitudinal relationships, the way I got to know my cancer patients’ families and passions that helped me realize I had found my calling.

Elizabeth Graham is a PBN contributing writer.