Abstract PS6-61: Survivin immunoexpression: An independent prognostic marker of recurrence in early-stage breast cancer
Authors: Belchior Heloisa OM , Andrade Victor P , Lima Marcos VA , do PSS Cunha Maria , Lemos Monique BC , Silva Paulo GB , Silva-Fernandes Isabelle JL 
Published: February 2021

Survivin is a small protein member of the inhibitor of apoptosis protein family. Its expression occurs in G2/M phase of cell cycle, acting inhibiting apoptosis blocking caspases cascade directly or indirectly, and also controlling cell division. Survivin was found to be overexpressed in breast cancer, and its expression have been associated mostly with poor outcome. The aim of this case-control study was to evaluate the prognostic value of Survivin immunoexpression in early stage (pT1pN0 or pT2pN0) breast cancer. The study was conducted collecting data from 170 women with invasive breast carcinoma. The case group (n=57) and control group (n=113) consisted of patients with and without tumor recurrence, respectively. Immunohistochemical Tissue Microarray analyses were conducted to detect Survivin expression. In addition, molecular classification was done based on immunohistochemistry, and classic clinical and histological breast cancer variables were collected. The findings were submitted to the chi-square test and Fisher’s exact test, followed by multivariate analysis with multinomial logistic regression. The level of statistical significance was set at 5% (p&lt;0.05). Median follow-up time was 6 years, ranging from 4 to 13 years. In the univariate analysis, patients with recurrence presented a higher histologic grade (p=0.005), percentage of tumor cells expressing survivin (p=0.006) and stronger immunostaining for this protein (p=0.021). In the multivariate analysis, stronger immunostaining for survivin (OR 1.850; p=0.023) and greater percentage of survivin expression (OR 2.290; p=0.016) persisted independently associated which higher rates of recurrence. Higher immunoexpression of survivin was independently associated with recurrence in early stage invasive breast tumors.

Multinomial logistic regression model. In the first model, variables with p &lt;0.200 were used in order to highlight the first order factors independently associated with disease-free survival. In the second model, variables with a significant association in model 1 were excluded in order to highlight second order factors independently associated with disease-free survival. In the third model, there were no factors independently associated with disease-free survival.

Table 1 - Clinical-pathological characterization of the 170 cases of early stage breast cancer patients with and without recurrence.RecurrenceTotalNoYespAge≤ 55 years8658280,78650,6%51,3%49,1%&gt; 55 years84552949,4%48,7%50,9%Histological subtypeDuctal158104540,24492,9%92,0%94,7%Lobular5502,9%4,4%,0%Others7434,1%3,5%5,3%StagespT1a7520,9024,1%4,4%3,5%pT1b2113812,4%11,5%14,0%pT1c65452038,2%39,8%35,1%pT277502745,3%44,2%47,4%Histological gradeI332850,00519,4%24,8%8,8%II75492644,1%43,4%45,6%III41192224,1%16,8%38,6%Ignored2117412,4%15,1%7,0%Breast surgeryMastectomy8557281,00050,0%50,4%49,1%Conservative85562950,0%49,6%50,9%Sentinel lymph node biopsyNo3220120,35318,82%17,7%18,2%Yes137934481,5%82,3%80,0%Ignored1010,6%0,0%1,8%ChemotherapyNo5135160,69730,0%31,0%28,1%Yes119784170,0%69,0%71,9%TrastuzumabNo156105510,76192,3%92,9%91,1%Yes13857,7%7,1%8,9%Hormone therapyNo2918110,58117,1%15,9%19,3%Yes141954682,9%84,1%80,7%

Table 2 - Patterns of Survivin expression in tumors of patients with breast cancer with and without recurrence.RecurrenceTotal**NoYespSubcellular localizationAbsent4220,9422,7%2,1%3,8%Cytoplasmic89573260,1%60,0%60,4%Nuclear2315815,5%15,8%15,1%Cytoplasmic and Nuclear32211121,6%22,1%20,8%IntensityAbsent4220,0212,7%2,1%3,8%Weak7353*2049,3%55,8%37,7%Moderate62382441,9%40,0%45,3%Strong927*6,1%2,1%13,2%Percentage of expression≤ 50%10977320,00673,6%81,1%60,4%&gt; 50%39182126,4%18,9%39,6%*p&lt;0,05** 22 patients (12,9%) of sample loss in tissue microarray.

Table 3 - Cox survival regression model of patients diagnosed and treated for invasive breast carcinoma.p-ValorAdjusted ORModel 1Histological grade*0,0072,108Survivin - intensity*0,0231,850Survivin - percentage of expression0,1001,876Breast cancer subtype classified by immunohistochemistry0,2631,126Model 2Survivin - percentage of expression*0,0162,290Breast cancer subtype classified by immunohistochemistry0,0931,170Model 3Breast cancer subtype classified by immunohistochemistry0,2411,107

Citation Format: Heloisa OM Belchior, Victor P Andrade, Marcos VA Lima, Maria do PSS Cunha, Monique BC Lemos, Paulo GB Silva, Isabelle JL Silva-Fernandes. Survivin immunoexpression: An independent prognostic marker of recurrence in early-stage breast cancer [abstract]. In: Proceedings of the 2020 San Antonio Breast Cancer Virtual Symposium; 2020 Dec 8-11; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2021;81(4 Suppl):Abstract nr PS6-61.