Abstract P4-12-11: Clinically occult primary breast cancer with regional lymph nodes metastasis: Management and prognostic factors
Authors: Zuhour Raed , Haque Waqar , Messer Jay , Lewis Gary , Chevli Neil , Teh Bin , Butler E. Brian , Farach Andrew , Hatch Sandra 
Published: March 2020

Background: Clinically occult primary breast cancer (COBC) with regional lymph nodes metastasis is a rare entity, with only 0.1% of breast cancer cases presenting in this fashion. The rarity of this entity precludes its study in a prospective manner. Cancer database registries offer a unique opportunity to study COBC and evaluate various management strategies and prognostic factors. Different treatment paradigms exist, including lymph node dissection, mastectomy, radiation alone, and chemotherapy. The purpose of this study is to determine the optimal treatment paradigm for patients with COBC.

Methods: The National Cancer Database (NCDB) was queried for patients with clinically occult breast cancer (cT0) and positive lymph node metastasis (cN1-3). Multivariate Cox Proportional Hazard modeling was used to determine factors independently associated with overall survival (OS). Sensitivity analysis was utilized to determine the optimal number of lymph nodes to be removed and the benefit of primary breast surgery (PBS) for patients who also received radiation therapy.

Results: A total of 2713 female patients were diagnosed with stage cT0N1-3M0 breast cancer from 2004 to 2015. 758 patients with missing data were excluded, and 1955 patients remained in the analysis. Results are shown in Table 1. Median follow-up was 48.1 months. Patients who were treated with chemotherapy, radiation therapy and/or had 4 or more lymph nodes removed had better OS (p&lt;0.05 for all). Sensitivity analysis did not reveal a survival advantage to removing more than 4 lymph nodes, compared to a more extensive axillary dissection of ≥ 10 lymph nodes. PBS, either with mastectomy or breast conserving surgery (BCS), without radiotherapy did not significantly improve overall survival. Sensitivity analysis did not demonstrate an OS benefit for mastectomy/BCS patients who also received radiotherapy. Endocrine therapy did not significantly impact OS.

Table 1: Multivariate Cox Proportional Hazard modeling results for COBC patientsVariablen (binary variables only)Hazard ratio95% CIp-valueAge-1.031.02-1.04&lt;0.001No comorbidities16310.700.55-0.890.003ER+12010.710.51-0.970.034PR+9290.750.58-0.990.042Clinical nodal stage-1.331.13-1.570.001Chemotherapy15960.650.50-0.860.002Nodes removed 4-93380.480.33-0.70&lt;0.001Nodes removed ≥1012630.490.36-0.67&lt;0.001Endocrine therapy10360.970.73-1.300.858Number of positive lymph nodes-2.722.08-3.55&lt;0.001Mastectomy with adjuvant radiotherapy5010.640.47-0.880.006BCS with adjuvant radiotherapy2020.470.30-0.730.001Radiotherapy without PBS5850.440.32-0.60&lt;0.001Mastectomy without adjuvant radiotherapy3320.760.54-1.060.102BCS without adjuvant radiotherapy300.460.17-1.260.131

Discussion: Definitive treatment of COBC with chemotherapy and radiation therapy is associated with improved OS. No survival advantage can be discerned for mastectomy or breast conserving surgery (alone or in conjunction with radiotherapy). While the survival advantage for endocrine therapy was not significant, that is likely due to short follow-up intervals. Sensitivity analysis revealed an incremental benefit for removing up to 4 lymph nodes. More extensive axillary lymph node dissections with ≥10 lymph nodes removed did not significantly improve OS.

Citation Format: Raed Zuhour, Waqar Haque, Jay Messer, Gary Lewis, Neil Chevli, Bin Teh, E. Brian Butler, Andrew Farach, Sandra Hatch. Clinically occult primary breast cancer with regional lymph nodes metastasis: Management and prognostic factors [abstract]. In: Proceedings of the 2019 San Antonio Breast Cancer Symposium; 2019 Dec 10-14; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2020;80(4 Suppl):Abstract nr P4-12-11.