What neoadjuvant therapy would you choose for a post menopausal woman with ER negative, PR positive high grade node negative breast cancer?

Assuming that there is no reason to doubt the results of the hormone receptor testing, and her HER2 is negative, I would treat her the same way I would a triple-negative cancer—I would not bother to send Oncotype as it should be high with the negative ER, and I wouldn't believe it if it came back low or low-intermediate. If her tumor is >2 cm (stage II), I favor weekly paclitaxel with carboplatin (either weekly AUC 2 or q3week AUC 5, though I prefer the weekly schedule to reduce hematologic toxicities and the likelihood of having to delay or modify treatment; in any case, do your best to get the 12 doses of weekly paclitaxel with carboplatin in to optimize pCR and EFS—evident in both CALGB 40603 and KEYNOTE-522) followed by AC—the addition ...

Most hormone-responsive breast cancers are either ER positive and PR positive, or ER positive and PR negative. Tumors that are ER negative and PR positive are unusual. I would first obtain assurance from the laboratory that quality control for hormone receptor testing was rigorously followed (proper tissue handling, fixation, presence of appropriate positive and negative controls). I would obtain genomic testing, acknowledging that there is less data for interpreting the results in this unusual subtype. I would combine the genomic profile with clinical and pathological factors (size of tumor, age of patient, comorbidities) in making this decision. Assuming the tumor is HER2 negative and more than 1 cm, that the patient has a good performanc...

@Dr. First Last makes a key point from the ABC trials in that TC was inferior to dose dense AC followed by paclitaxel in node positive triple negative patients (this patient essentially is triple negative).

For that reason, I tend to avoid TC as neoadjuvant treatment even in small tumors, as I'm not sure of the nodal status of the patient. Even in a clinically negative axilla, the risk of positive SLN biopsy can approach 30% (see NSABP-32), although the number is probably not as high for very small tumors < 1 cm and when MRI breast is utilized. Also, neoadjuvant TC is less well studied, and the study showed inferior outcomes compared to neoadjuvant anthracycline based regimen in one trial (see NATT trial).

In pre-COVID-19, I had been asking o...

The expression of PR receptor is dependent on the Estrogen pathway. The presence of PR in the absence of ER either implies a false neg ER or a false positive PR (IHC). Retesting IHC on a different specimen should help. Prognostic outcomes for ER- and PR+ cancers are intermediate between ER+ and triple negative cancers, thus confirming a mix of true ER+ and triple negative cases.

Genomic assay, like recurrence risk, rely on PCR based assay for ER, and can have discordant results to IHC.

I have used the 21 gene assay if otherwise applicable (node neg, low Ki67 etc), and I get a PCR based ER status on the report. This is my approach to weed out the false positives and the false negatives. The 70 gene assay panel would not be applicable here s...

Agree with @Dr. First Last.

If the tumor is T1a and HER2 negative and Ki 67 is below 20...observation is another option, as with some T1a triple negative tumors (assuming the neoadjuvant part is due to COVID-19 and not due to tumor related reasons). Also at this time, I would prefer TC rather than 12 weeks of paclitaxel-Carbo (assuming that tumor is in fact node negative on SLNB), due to a reduced need for visits.