Standard Pathologic Features Can Be Used to Identify a Subset of Estrogen Receptor-Positive, HER2 Negative Patients Likely to Benefit from Neoadjuvant Chemotherapy

Abstract

Background The benefit of neoadjuvant therapy (NAC) in patients with estrogen receptor positive (ER+) HER2− breast cancers and in invasive lobular cancer (ILC) is uncertain due to low rates of pathologic complete response (pCR). Our aim was to determine if pathologic features can identify subsets likely to benefit from NAC. Methods Patients with stage I–III ER+, HER2− breast cancer receiving NAC were retrospectively reviewed. Endpoints were downstaging to breast-conserving surgery (BCS) and nodal pCR after NAC. Patients were grouped by progesterone receptor (PR) status and grade/differentiation (high grade or poor [HP] vs non-HP). Results From 2007–2016, 402 ER+/HER2− cancers in patients receiving NAC were identified. Median age was 50 years, 98% were clinical stage II–III, and 75% cN+. Overall pCR rate was 5%; breast pCR in 7%, nodal pCR in 15% of cN+ patients (p<.0001). Patients with ILC initially ineligible for BCS (n=56) were less likely to downstage than those with ductal (n=183), 16% vs 48% (p≤.0001); with a similar trend in the axilla (p=.086). Rates of BCS eligibility after NAC were highest in PR−/HP (62%) and lowest in PR+/non-HP (29%) patients (p=.005). In the axilla, nodal pCR among cN+ patients (n=301) ranged from 0–35% (p<.0001) within these groups, and was most frequent in PR−/HP patients. Conclusions ER+/HER2− patients most likely to benefit from NAC are those with PR− and HP tumors. Patients with ILC are unlikely to downstage in the breast or axilla compared to IDC. Use of these criteria can assist in defining initial treatment approach.

Unifocal Invasive Lobular Carcinoma: Tumor Size Concordance Between Preoperative Ultrasound Imaging and Postoperative Pathology

“…Receptor status 25,26 in conjunction with extent of disease 24 is important when considering neoadjuvant therapy for ILCs, especially when breast conservation is considered 24,27–29 . Breast ultrasound is a widely available modality and can be used as a complement to further characterize lesions.…”

“…This is important in the context of neoadjuvant therapy. Among patients who undergo neoadjuvant chemotherapy, pathologic complete response rate is lower with ILCs than ductal cancers 24,25 and is dependent on receptor status 25,26 . However, neoadjuvant chemotherapy, in particular for clinically-assessed T2 and T3 ILCs, can be of benefit in facilitating breast conserving surgery 24 .…”

“…However, neoadjuvant chemotherapy, in particular for clinically-assessed T2 and T3 ILCs, can be of benefit in facilitating breast conserving surgery 24 . Accurate measurement of tumor size in combination with receptor status 25,26 can help in identifying subjects that are likely to benefit from breast conservation following neoadjuvant chemotherapy. Hence, we conducted this systematic retrospective analysis in subjects diagnosed with unifocal ILC.…”

The impact of chemotherapy sequence on survival in node‐positive invasive lobular carcinoma

“…As a result, neoadjuvant chemotherapy (NACT) is not infrequently recommended for patients with ILC. But ILC is also nearly always hormone receptor (HR)‐positive, and previous studies have demonstrated that patients with low‐grade, HR‐positive (HR+) ILC have a poor response to NACT, experiencing lower rates of pathologic complete response (pCR) than patients with IDC . Concomitantly, NACT has historically been less successful in enabling breast conservation or omission of more extensive axillary surgery among ILC patients, who have higher rates of mastectomy and completion axillary lymph node dissection (ALND) than those with IDC .…”

“…hormone receptor (HR)-positive, and previous studies have demonstrated that patients with low-grade, HR-positive (HR+) ILC have a poor response to NACT, experiencing lower rates of pathologic complete response (pCR) than patients with IDC. [5][6][7] Concomitantly, NACT has historically been less successful in enabling breast conservation or omission of more extensive axillary surgery among ILC patients, who have higher rates of mastectomy and completion axillary lymph node dissection (ALND) than those with IDC. [8][9][10][11] Nevertheless, similar criteria-including nodal involvement-are used to determine whether NACT should be administered in both histologic subtypes.…”