Is There a Role for Oncotype Dx Testing in Invasive Lobular Carcinoma?

Abstract

Oncotype Dx Breast Cancer Assay is a 21-gene assay used in estrogen receptor (ER)-positive breast cancer to predict benefit from chemotherapy (CT). Tumors are placed into one of three risk categories based on their recurrence score (RS). This paper explores the impact of tumor histopathologic features and Oncotype Dx RS on the treatment plan for invasive lobular carcinoma (ILC). Invasive lobular carcinoma cases submitted for Oncotype Dx testing were identified from a clinical data base. The histopathologic and immunohistochemical features and RS subcategory of each tumor, and treatment regimen and medical oncologic assessments of each patient were reviewed. A total of 135 cases of ILC had RS testing, which represented 15% of all ILC diagnosed at the institution over the time period. 80% of ILC was of the classical subtype and all tumors were ER positive and human epidermal growth factor receptor 2 (HER-2) negative by immunohistochemistry. Sixty three percent of cases were low risk (LR), 35.5% were intermediate risk (IR) and 1.5% were high risk (HR). Both HR cases were pleomorphic ILC. Sixty eight percent of classical ILC had a LR score, while 70% of pleomorphic ILC had an IR score. Patients in the IR category were significantly more likely to undergo CT than patients in the LR category (54% versus 18%; p < 0.0001). In the LR category, those undergoing CT were significantly younger and more likely to have positive lymph nodes (p < 0.05). Qualitative analysis of medical oncologic assessments showed that RS played a role in decision-making on CT in 74% of cases overall. At our institution, Oncotype Dx RS currently plays a role in the management of a proportion of ILC and impacts on treatment decisions.

Breast cancer histopathology is predictive of low-risk Oncotype Dx recurrence score

“…3,5,7 Histologic subtype is known to affect prognosis but it is not taken into account when patients are considered for Oncotype Dx testing. [8][9][10] Bomeisl et al demonstrated that "good prognosis" histologic subtype together with ER, PR, HER2, and lymph node status could be used for assessing risk in the absence of Oncotype Dx testing. 8 (Table S1) but did not diminish the predictive power of histologic subtype and grade.…”

“…Several studies have shown a relationship between ORS and traditional prognostic markers like histologic grade, tumor size, hormone receptor status, lymph node status, and Ki-67 proliferation index. [3][4][5][6][7][8][9][10] In this study, we investigate whether certain histologic subtypes can be identified that may not benefit from OncotypeDx ® testing. Invasive carcinomas were graded according to the Elston and Ellis modification of the Nottingham grading system based on the extent of tubule formation, nuclear grade, and mitotic count (grade I: total score 3-5, grade II total score 6 or 7, and grade III total score 8 or 9).…”

Differences between invasive lobular and invasive ductal carcinoma of the breast: results and therapeutic implications

“…Similar to IDCs, approximately 40% of ILCs have an intermediate RS. Of relevance, Conlon and colleagues showed that in pleomorphic ILC cases, the proportion of tumors with intermediate RS may even be higher compared with classical ILC (69 × 32%, respectively) [Conlon et al 2015]. Until the results of prospective trials (such as the MINDACT or TAILORx trial) are available, the optimal management of the intermediate RS group remains unestablished.…”

Relative effectiveness of adjuvant chemotherapy for invasive lobular compared with invasive ductal carcinoma of the breast

“…The genomic profile of ILCs is also different from that of ER‐positive/HER2 negative IDCs. The 21‐gene recurrence scores (RS) for ILCs are rarely categorized as high risk, whereas approximately 8% to 15% of ER‐positive/HER2‐negative IDCs are categorized as high risk . In addition, the pathologic complete response (pCR) rates after neoadjuvant chemotherapy are substantially lower for ILC compared with ER‐positive/HER2‐negative IDC .…”

“…The 21-gene recurrence scores (RS) for ILCs are rarely categorized as high risk, whereas approximately 8% to 15% of ER-positive/HER2-negative IDCs are categorized as high risk. [4][5][6] In addition, the pathologic complete response (pCR) rates after neoadjuvant chemotherapy are substantially lower for ILC compared with ER-positive/HER2-negative IDC. [7][8][9][10][11] Also, the relative effectiveness of letrozole compared with tamoxifen is higher for ILC versus IDC.…”