Coordinated Care in Breast Oncology: Systemic Therapy Trials and Personalized Approaches

In this episode of OncChats: Coordinated Care in Breast Oncology, Jason Ye, MD, and Daphne B. Stewart, MD, of Keck Medicine of USC, explore how advances in systemic therapy—including novel agents, genomic profiling, and national trials—are helping personalize and de-escalate breast cancer treatment.

Ye: And actually, in fact, a lot of these de-escalation and radiation [approaches are] made possible because of improvement in systemic therapy. I’d love to hear a little bit about the systemic therapy trials, too.

Stewart: Yes, so here, at USC, we have a number of trials that are both prior to surgery to be able to de-escalate therapy and then post-surgery to potentially de-escalate therapy. We have a lot of clinical trials, but I just want to focus on these two categories. We have a collaborative study called [the phase 2] I-SPY [NCT01042379]. This is a trial that’s been on board since 2012 and there have been more than 4000 patients enrolled. It focuses on the introduction of new chemotherapy agents that are approved in the metastatic breast cancer setting because they’re effective, but they’re moved forward into the neoadjuvant setting, thinking that they are more effective than standard chemotherapy. The enrollment in I-SPY allows patients to be exposed to really, really positive agents that are less toxic than our standard chemotherapy and may actually lead [them] to a higher rate of complete remission of cancer with a systemic therapy. [It] may also permit early escalation to surgery that doesn’t take a 6-month treatment intervention; maybe at 3 months, [a patient has] enough of a treatment response that [they’re] able to go directly to surgery. It gives us a whole aspect of how to improve our systemic therapies when we give it before surgery, to see how all those different subtypes of breast cancer can be maximized. We’re really, really motivated to do this.

We have another couple of clinical trials that are looking specifically at [the question of,] how we can optimize shrinking tumors before [a patient goes] to surgery? Specifically, there is a study using a novel antibody-drug conjugate with novel immunotherapy up front compared with our standard chemotherapy, which has been associated with a really significant clinical response rate and better [tolerability with] fewer [adverse] effects. It really makes sense, and again, when we introduce it [to] the multidisciplinary [discussions], we can actually talk about what the benefit is. Why would we be doing treatment before [a patient goes] to surgery? Again, to try to shrink the tumor and limit the risk of any micrometastatic disease.

In the adjuvant setting, which Dr Ye, was talking about, once [a patient undergoes] up-front surgery, let’s say [they] have a lower-risk breast cancer where it’s an estrogen receptor [ER]–positive tumor that’s maybe less than 3 cm and maybe has one to two positive lymph nodes; these are the kind of patients who undergo genomic profiling. Typically, we use the Oncotype [DX test], or we use the MammaPrint, which are gene profiles that help estimate the risk of recurrence—specifically metastatic recurrence—and the benefit to chemotherapy. There’s a lot of controversy in terms of the use of adjuvant chemotherapy in patients who have ER-positive breast cancer. If [a patient has] a very high-risk profile on that gene profile, we know that there’s a benefit to chemotherapy, and that represents around 30% of all of the patients; however, there’s still going to be a component in that 70% that probably does benefit from chemotherapy, and the ones that we think are going to benefit the most are premenopausal patients with ER-positive breast cancer that probably benefit from chemotherapy because they enter a premature menopause which suppresses their estrogen and lowers their risk of a breast cancer recurrence.

We have a really interesting, activated study here. Again, it’s a collaborative trial that has opened across the country, and what we’re specifically looking at are premenopausal women with ER-positive breast cancer who are considered intermediate risk for recurrence; they’re not low risk and they’re not high risk but they’re in that gray zone. That trial is going to randomly assign patients to simply putting them into early menopause using gonadotropin-releasing hormone agonists and antagonists to make sure that you suppress ovarian function, and then give the aromatase inhibitors, which are the postmenopausal treatment of ER-positive breast cancer vs chemotherapy, followed by additional ovarian function suppression. This trial is aiming to recruit at least 4000 patients over the next 5 years. We’re contributing to these international sites because what we’re trying to identify is, are patients really benefiting from chemotherapy or if the chemotherapy is inducing the menopause. I think this is a really important trial, and we are able to identify potential candidates for this study during these multidisciplinary interactions.

Ye: Yes, and these are really important questions for us to know going forward.

Check back on Monday for the next episode in the series.