Applying NCCN Guidelines for Pre- and Post-Menopausal Breast Cancer

Hormone receptor-positive, HER2-negative is the most common subtype breast cancer, and its treatment is guided by genomic testing and clinical factors to determine the need for chemotherapy, endocrine therapy and aromatase inhibition (AI). Neil M. Iyengar, MD, director of survivorship services at Winship Cancer Institute of Emory University and associate professor and co-director of the Breast Medical Oncology Program in the Department of Hematology and Medical Oncology at Emory University School of Medicine, discussed the standard of care in the NCCN guidelines at a live event in New York. Iyengar detailed the use of the 21-gene recurrence score to stratify risk and guide adjuvant treatment decisions in premenopausal and post-menopausal patients.

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CASE SUMMARY

• A 52-year-old woman presented with a mass in the left breast on routine mammogram.
• Mammogram/ultrasound showed a 1.9-cm mass.
• Core biopsy showed invasive ductal carcinoma (IDC), grade 3; estrogen receptor 80%, progesterone receptor 25%, HER2 immunohistochemistry < 1; 21-gene recurrence score 25; Ki-67 25%
• Sentinel lymph node biopsy negative for IDC
• Germline testing negative for pathogenic variants
• She underwent left mastectomy.
• 2.1-cm IDC, grade 3
• Anatomic stage: T2 pN0 M0 / IIA

Targeted Oncology: What do the NCCN guidelines recommend for a patient with breast cancer such as this if she were post-menopausal?

Neil M. Iyengar, MD: For our highest risk patients with high nodal burden, these are the patients [to whom] we're giving chemotherapy, endocrine therapy, and AI, typically for our postmenopausal patients. The NCCN does indicate select patients may be eligible for treatment with abemaciclib [Verzenio], ribociclib [Kisqali], and PARP inhibition if they have a germline BRCA1 or BRCA2 mutation.

Our patients who have 1 to 3 positive notes or microscopic involvement of a lymph node, where we need to get into genomic risk stratification. We use our 21-gene signature test, and as we know from TAILORx [NCT00310180], a score of 26 or greater indicates adjuvant chemotherapy followed by endocrine therapy. We have a similar statement [in the guidelines to] consider abemaciclib or ribociclib for eligible patients. We know the eligibility criteria are different for these 2 drugs.

If the recurrence score is under 26, we know from TAILORx that that population did not derive the benefit from chemotherapy, and so we would omit chemotherapy and proceed to endocrine therapy with a CDK4/6 inhibitor. For our small tumors [measuring] less than half a centimeter, we're going straight to endocrine monotherapy there.

For the premenopausal population, what does the NCCN suggest?

This is where we need to dissect the TAILORx trial a little further. We're focused on our premenopausal N0 population. We know for our node-positive premenopausal population, the genomic risk stratification was not able to rule out a benefit of chemotherapy. The current standard of care in node positive premenopausal population remains the use of adjuvant chemotherapy. Of course, there are nuances there, but that is the umbrella approach. But for our N0 patients here, this is where we get into this risk stratification. So we're talking N0, T1b to T3; in other words, a tumor size greater than half a centimeter, and you order your genomic risk score. In TAILORx, it was the Oncotype DX score.

Starting with our highest-risk patients, for a score of 26 or above, we're using chemotherapy. NCCN lists ribociclib for eligible patients. Remember, these are N0 patients, where ribociclib from the NATALEE trial [NCT03701334] was the only adjuvant CDK4/6 inhibitor trial to include that N0 population here, hence the NCCN recommendation. In TAILORx, the benefit of chemotherapy in the N0 premenopausal population could not be ruled out for those patients who had recurrence scores of 16 to 25 and so in that population, you could offer chemotherapy. I generally do offer chemotherapy.

Do you feel like the ranges used in TAILORx and the NCCN are accurate to guide treatment in these patients?

I can understand for convenience’s sake why it was done this way, but if you look at the statistical analysis in TAILORx, it wasn't categorical analysis. These categories were not predefined, so there is a continuum. For our premenopausal patients who have a recurrence score of 24, that's different than a patient who has a recurrence score of 17. But just for ease, we have the NCCN listing that [between] 16 to 25 you would consider chemotherapy.

Then maybe patients in that lower range who you will not recommend chemotherapy for if their score is 15 or below [go] straight to adjuvant endocrine therapy with or without ovarian suppression. That is also part of the discussion in our premenopausal patients, because that now impacts our use of CDK4/6 inhibitor. If you're using tamoxifen in this population, you cannot use ribociclib. And if you do want to use ribociclib, then that impacts your hormone therapy decision making. In other words, you need to pull the trigger on ovarian suppression in order to use the AI.

This is where I think the conversation starts to get complex with our patients. I go back to looking at those ranges and where they fall in that range so we can have a discussion for what sways you one way or the other. We'll learn more soon, because we will see data that help to address the question of, is the chemotherapy what's helping for those patients with that 16 to 17 recurrence score or is it the ovarian suppression effect of the chemotherapy that's driving a potential benefit there. We'll have those data soon, and we may be in a world wherein those with scores of 16 to 25 may [be able to] go straight to endocrine therapy, as long as you're using ovarian suppression. For now, it's a bit of a complex discussion.

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DISCLOSURES: There are no known disclosures.

Reference:

NCCN. Clinical Practice Guidelines in Oncology. Breast cancer; version 4.2025. Accessed September 4, 2025. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf