Abstract P2-09-01: Clinicopathological features and surgical management trends in individuals with breast cancer and deleterious mutations in moderate penetrance genes
Authors: Pence Colton , Berg Jordan , Partain Natalia , Sadeghi Navid , Mauer Caitlin , Pirzadeh-Miller Sara , Gao Ang , Li Hsiao , Unni Nisha , Syed Samira 
Published: March 2020

Background: Moderate penetrance genes - ATM, CHEK2, and PALB2 - are often included in hereditary cancer panel testing as mutations have been linked to familial breast cancer. Limited data exists on breast cancer presentation and surgical management. We aimed to review clinicopathological features of breast cancers in patients affected by these mutations and trends in surgical management compared to unaffected cancer patients. Methods: We conducted a retrospective review of breast cancer patients, stage 0 to III, with deleterious mutations in ATM, CHEK2, and PALB2 between 2007 and 2017 at a tertiary institution. Data collected included demographics, clinicopathological tumor features, and type of treatment. These patients were compared to a control group of sporadic breast cancer patients referred for genetic counseling who tested negative for deleterious mutations via panel testing. Chi-square test, t-test, and stepwise logistic regression were used for statistical analysis. Results: A total of 145 patients had breast cancer (144 women and 1 male). There were 74 mutation-positive patients (24 ATM, 26 CHEK2, 24 PALB2) and 71 mutation-negative patients (Table 1). No differences were found in age or ethnicity among both groups. Mutation-positive patients had a higher rate of family members affected by breast cancer (79.7% vs. 52.9% in mutation-negative, p=0.0006), and tumors greater than 2 cm (63.1% vs. 42.3% in mutation-negative, p=0.0152). No differences were found on tumor histopathology, use of radiotherapy, and use of chemotherapy/endocrine therapy between the two groups. Of the patients harboring mutations, 55 patients received surgical treatment for their breast cancer after discovery of their mutation status, while the rest had surgery performed prior to genetic testing. All controls received surgery as part of treatment. Significant differences were seen in type of surgery chosen in each group. There was a lower rate of breast-conserving surgery in the mutation-positive group (25.5% vs. 46.5% in mutation-negative, p=0.0155). Additionally, 65.5% of mutation-positive patients underwent contralateral prophylactic mastectomy (CPM) compared to 33.3% in mutation-negative patients (p=0.0004). There was no association between age or ethnicity and choice of CPM. Conclusions: Mutation-positive patients are more likely to have positive family histories and larger tumors at diagnosis. They also have a higher rate of mastectomy and double the rate of CPM compared to those unaffected by mutations in moderate penetrance genes. These patients opt for more radical surgical treatment despite lack of clear guidelines for this approach. Further studies are needed to better advise physicians and patients regarding treatment decisions when encountering these mutations.

Table 1. Patient, tumor, and treatment characteristicsMutationaNo mutationN=74N=71P-valueAge at diagnosis, mean (SD)48.43 (10.47)50.82 (9.84)0.1601no. (%)no. (%)EthnicityWhite49 (66.2)45 (63.4)0.8839Hispanic15 (20.3)13 (18.3)Black8 (10.8)11 (15.5)Asian2 (2.7)2 (2.8)Family history of breast cancerbYes50 (79.7)37 (52.9)0.0006No15 (20.3)33 (47.1)Stagec0 and I23 (33.8)35 (49.3)0.0644II and III45 (66.2)36 (50.7)Tumor sizec (cm)≤ 224 (36.9)41 (57.7)0.0152&gt; 241 (63.1)30 (42.3)Lymph nodecPositive24 (36.4)26 (36.6)0.9752Negative42 (63.6)45 (63.4)Nuclear gradeI9 (15.8)14 (20.0)0.8284II23 (40.4)27 (38.6)III25 (43.9)29 (41.4)Estrogen receptorPositive56 (84.8)53 (74.6)0.1390Negative10 (15.2)18 (25.4)HER2/Neu receptorPositive17 (26.2)14 (19.7)0.3715Negative48 (73.8)57 (80.3)HistologyDuctal69 (93.2)63 (88.7)0.3419Lobular5 (6.8)8 (11.3)KI-67 proliferation index≤ 2017 (34.0)22 (36.7)0.7710&gt; 2033 (66.0)38 (63.3)Use of chemotherapyYes47 (67.1)45 (63.4)0.6390No23 (32.9)26 (36.6)Adjuvant radiotherapyYes42 (59.2)40 (56.3)0.7340No29 (40.8)31 (43.7)Adjuvant endocrine therapyYes45 (65.2)53 (74.6)0.2235No24 (34.8)18 (25.4)Type of surgeryBCSd14 (25.5)33 (46.5)0.0155TMd41 (74.5)38 (53.5)Contralateral prophylactic mastectomy (CPM)CPM36 (65.5)23 (33.3)0.0004No CPM19 (34.5)46 (66.7)(a). ATM, CHEK2, PALB2, (b) First and second-degree relatives, (c) Tumor size, lymph node status, and stage assessed clinically, (d) Abbreviations: BCS = breast-conserving surgery, TM = total mastectomy

Citation Format: Colton Pence, Jordan Berg, Natalia Partain, Navid Sadeghi, Caitlin Mauer, Sara Pirzadeh-Miller, Ang Gao, Hsiao Li, Nisha Unni, Samira Syed. Clinicopathological features and surgical management trends in individuals with breast cancer and deleterious mutations in moderate penetrance genes [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 P2-09-01.