HR+ Breast Cancer: Future Treatment Opportunities


Guidance on how to treat a 67-year-old patient with ER-positive/PR-positive breast cancer, and additional therapies in the pipeline that have the potential to improve treatment.

Kevin Kalinsky, MD, MS: For this particular patient, she would have had surgery first. Commonly, we give chemotherapy next, and then we give radiation, then we give hormonal therapy.

There is no safety concern about giving the hormonal therapy with the radiation, but it’s more if there are toxicities. It’s good to know when it’s due to, as opposed to having 2 things going on at 1 time.

I tend to start the aromatase inhibitor and then add on the abemaciclib after a few months, just demonstrating that they are tolerating it. And that’s again, just because I don’t want there to be a confounding factor.

And monarchE patients had 16 months before they needed to start their abemaciclib. So we don’t need to urgently initiate the abemaciclib.

Which is why I tend to start it just after we know that the patient’s taking the aromatase inhibitor and they’re adherent, and then I start the abemaciclib for 2 years. And then I continue that aromatase inhibitor after that.

There is an important distinction in terms of the timing that we see relapse. So if we see a patient that’s recurring on the abemaciclib and the aromatase inhibitor, this would give some concern, and I would think, the patient’s resistant to those medicines.

And I would think about switching that particular patient to fulvestrant-based therapy. And I’d have some reservations about giving them a CDK4/6 inhibitor, especially if they’re recurring on Verzenio. And that’s a little bit different than somebody who received their abemaciclib, goes on to get an aromatase inhibitor, and then, let’s say, 3 years later recurs.

In that particular situation, I would feel more comfortable about potentially utilizing an aromatase inhibitor and CDK4/6 inhibitor. And this field is moving so quickly that we really don’t have data about sequencing yet, but we’re awaiting some data in the metastatic setting about sequencing from some randomized phase 2 studies. And there’s a phase 3 trial that’s going to be addressing this question.

I do some genomics, and I do think that there’s a role for it, checking for ESR1 mutations. Commonly, that’s checked with circulating tumor DNA [ctDNA]. We know that patients who are taking aromatase inhibitors are less likely to benefit compared to something like fulvestrant [therapy]—the IM [intramuscular] injection of the SERD [selective estrogen receptor degrader] in the metastatic setting for patients who have ESR1 mutations.

But there’s an entire class of oral SERDs that are coming down the pike. In San Antonio, in 2020, we saw the results of the EMERALD study with Elacestrant, which demonstrated an improvement in progression-free survival with those who have ESR1 mutations; comparing that particular oral SERD with the standard of care, physician choice, anti-estrogen therapy.

So that’s not something that’s available in the clinic now, but I think moving forward, and hopefully soon, we’ll see oral SERDs as an option for patients.

I do think that, to me, what’s going to be exciting in the next few years are the oral SERDs. I do think that that’s going to be changing the landscape of how we treat patients in the metastatic setting and potentially in the early-stage setting as well.

I think the other unmet need for patients with early-stage disease is that the biology of this cancer is that we can see a late recurrence. So recurrences 10 to 20 years later.

And hopefully, we’ll identify predictors of late recurrence as well as ways to mitigate that, and the oral SERDs may have a place in that paradigm. I think that there’s a lot of excitement about circulating tumor DNA.

And there are some prospective retrospective studies suggesting their potential utility in the early-stage setting and there are some studies that are opening/open, that are specifically looking at, not just the prognostic implications of having ctDNA positivity, but also the potential predictive utility. Meaning, then you change the therapy, can you delay the risk of recurrence? And I think that that’s really where the field is going.

Transcript edited for clarity.

Case: A 67-Year-Old Woman with ER+/PR+ Breast Cancer

Initial Presentation

  • A 67-year-old, postmenopausal woman presents with a newly diagnosed lump in her left breast
  • She has 2 grown children, no family history of cancer, and underwent menopause at age 48
  • PMH is significant for hypertension that is well controlled with medication

Clinical work-up

  • Imaging demonstrated a 4.4-cm solid mass in the right upper quadrant with no suspicious adenopathy
  • Core biopsy: positive for invasive ductal carcinoma, ER 100%/PR 40%; HER2 IHC 1+; Ki-67 30%; modified Bloom-Richardson grade 3
  • Lumpectomy and sentinel lymph node biopsy performed
  • Tumor size is 4.5 cm, and 2/5 LNs are positive for metastatic disease
  • 21-gene recurrence assay score is 30
  • T2N1M0, stage IIA
  • ECOG PS is 0


  • Patient underwent partial mastectomy with no residual disease
  • She is started on adjuvant chemotherapy with cyclophosphamide and docetaxel
  • She is given radiation therapy to intact breast
  • Followed by aromatase inhibitor + 2 years of abemaciclib
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