Avoiding an Axillary Lymph Node Dissection: The Benefit of Neoadjuvant Chemotherapy for Occult Primary Breast Cancer

Past

The implementation of neoadjuvant chemotherapy (NAC) has changed the surgical landscape and is increasingly utilized among node-positive patients in attempt to de-escalate axillary surgery. Multiple trials have demonstrated the feasibility of sentinel lymph node biopsy (SLNB) following NAC,¹ and patients who convert from cN1 to cN0 following NAC and obtain a nodal pathologic complete response (pCR) may be eligible for SLNB alone. It is now well established that nodal pCR rates vary by receptor profile, and therefore the likelihood of minimizing extent of axillary surgery remains heavily influenced by tumor biology.^2,3 As the literature supporting axillary surgical de-escalation was based on patients with intact primary tumors, it is unknown whether similar rates of pCR would be seen among women with occult primary breast cancer (OPBC), a population historically felt to harbor heavier nodal disease burden. We sought to determine the frequency of nodal pCR following NAC, and thus the potential omission of ALND, in a cohort of patients with OPBC.

Present

Twenty biopsy-confirmed OPBC patients were identified at Memorial Sloan Kettering Cancer Center from 2008–2019, all of whom received NAC. Most (75%) presented with cN1 disease, the remaining patients (25%) presented with cN2-N3. The tumor subtypes were as follows: 8 (40%) were triple negative, 6 (30%) were ER+/HER2-, and 6 (30%) were HER2+. Nodal pCR was achieved in 16/20(80%) of patients, including 3/6 (50%) ER+/HER2-, 7/8 (88%) TNBC, and 6/6 (100%) HER2+^.4 Among the 15 patients who presented with cN1 disease, 14 (93%) converted to cN0 following NAC. Of these, 9 underwent SLNB alone; all of whom achieved a nodal pCR. All women presenting with cN2-cN3 disease (n = 5) underwent an ALND; 3 remained pathologically node positive (pN+) and 2 achieved nodal pCR. Seventeen (85%) completed either whole-breast radiation therapy (WBRT) or postmastectomy radiation therapy with regional nodal irradiation. With a median follow-up of 38.5 months (range 4.3127.5) no recurrences have been reported.

Future

OPBC management has evolved from a modified radical mastectomy, to a breast conserving approach with ALND and WBRT.⁵ While ALND has been standard of care for OPBC patients, there are ongoing efforts to identify populations of node-positive patients who may safely avoid an ALND to minimize surgical morbidity. While ourstudyis limitedby relatively small numbers, the data highlight exceptional nodal pCR rates among women with OPBC treated with modern NAC regimens, supporting potential surgical de-escalation. The rates of nodal pCR varied by receptor profile, being lowest in the ER+/HER2- group and highest in the HER2+ group (50–100%); however, they are excellent and show consistency with those in the literature for women with an intact breast primary tumor. Given the excellent pCR rates observed, SLNB alone appears to be a feasible surgical option in select OPBC patients who downstage following NAC.⁴ Follow-up of this cohort will provide further data to support this approach.