Clinical Oncology Letters
http://www.col.periodikos.com.br/article/doi/10.4322/col.2018.006
Clinical Oncology Letters
Artigo Original

Change in immunohistochemistry biomarker profile after treatment correlates with prognosis in breast cancer patients

Mudança no perfil do biomarcador de imunohistoquímica após o tratamento correlaciona-se com o prognóstico em pacientes de câncer de mama

Vanessa Teixeira, Waldec Jorge David Filho, Auro del Giglio

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Abstract

Objective: To evaluate the prognostic implications of a change in Immunohistochemical profile (IP) versus no change in IP. Methods: We evaluated a total of 3982 consecutive patients with a history of BC treated at our Institution from January 1, 2008 to December 31, 2012 who had more than one biopsy for their first systemic, local Breast Cancer (BC) recurrence or after neoadjuvant chemotherapy. We selected patients who had at least one biopsy with a change in IP and considered only the first biopsy in which a change occurred. We excluded patients who had in situ carcinoma, men with breast cancer and women with de novo metastatic disease. We then matched each patient with two control patients whose IP remained unchanged during follow-up. Results: Patients whose IP changed had a mean age of 52.58 years. Initial and follow-up IPs were luminal A or B (36.8%; 42%), Her2 like (38%; 18%), Her2 (10%; 12.4%), and Triple negative (38%; 27,6%). Median follow-up time was 72 months. Two hundred and fifty patients changed IP during follow-up (6.28%, 95% CI 5.56 - 7.08) and fared better than those who did not change their IP (log rank = 13.49, p = 0.0002). According to multivariate analysis, non-luminal IP (RR=1,61, p =0.001) and stable IP (RR=1.65, p <0.0001) were significant independent variables associated with worse survival. Conclusion: We conclude that IP stability may portend a worse prognosis for BC patients after chemotherapy. Further studies are needed to confirm these findings and to elucidate the molecular mechanisms involved.

Keywords

Breast cancer; Immunohistochemistry; Prognosis

Resumo

Objetivo: Avaliar as implicações prognósticas de uma mudança no Perfil Imunohistoquímico (PI) versus nenhuma mudança no PI. Métodos: Avaliamos 3982 pacientes consecutivos com história de câncer de mama (CM) tratados em nossa instituição de 1 de janeiro de 2008 a 31 de dezembro de 2012 que tiveram mais de uma biópsia para sua primeira recidiva sistêmica, local ou após quimioterapia neoadjuvante. Selecionamos pacientes que tiveram pelo menos uma biópsia com alteração no PI e consideramos apenas a primeira biópsia em que ocorreu uma alteração. Foram excluídos pacientes com carcinoma in situ, homens com câncer de mama e mulheres com doença metastática de novo. Em seguida, comparamos cada paciente com dois controles, cujos PIs permaneceram inalterados durante o acompanhamento. Resultados: Pacientes cujo PI mudou tiveram média de idade de 52,58 anos. Os PIs iniciais e de acompanhamento foram luminal A ou B (36,8%; 42%), Her2 like (38%; 18%), Her2 (10%; 12,4%) e Triplo negativo (38%; 27,6%). O tempo mediano de acompanhamento foi 72 meses. Duzentos e cinquenta pacientes mudaram PI durante o acompanhamento (6,28%, IC95% 5,56-7,08) e se saíram melhor do que aqueles que não mudaram seu PI (log-rank = 13,49, p = 0,0002). Pela análise multivariada, PI não-luminal (RR = 1,61, p = 0,001) e IP estável (RR = 1,65, p <0,0001) foram variáveis independentes significativas associadas a pior sobrevida. Conclusão: A estabilidade do PI pode prenunciar pior prognóstico para pacientes com CM após a quimioterapia. Mais estudos são necessários para confirmar esses achados e elucidar os mecanismos moleculares envolvidos.

Palavras-chave

Câncer de mama; Imuno-histoquímica; Prognóstico

Referências

1. Criscitiello C, André F, Thompson AM, et al. Biopsy confirmation of metastatic sites in breast cancer patients: clinical impact and future perspectives. Breast Cancer Res. 2014;16(2):205. http://dx.doi.org/10.1186/bcr3630. PMid:25032257.

2. Van Poznak C, Somerfield MR, Bast RC, et al. Use of biomarkers to guide decisions on systemic therapy for women with metastatic breast cancer: american society of clinical oncology clinical practice guideline. J Clin Oncol. 2015;33(24):2695-704. http://dx.doi.org/10.1200/JCO.2015.61.1459. PMid:26195705.

3. Ozmen V, Atasoy A, Bozdogan A, Dincer M, Eralp Y, Tuzlali S. Prognostic value of receptor status change following neoadjuvant chemotherapy in locally advanced breast cancer. Cancer Treat Res Commun. 2015;4:89-95. http://dx.doi.org/10.1016/j.ctrc.2015.07.001.

4. Tacca O, Penault-Llorca F, Abrial C, et al. Changes in and prognostic value of hormone receptor status in a series of operable breast cancer patients treated with neoadjuvant chemotherapy. Oncologist. 2007;12(6):636-43. http://dx.doi.org/10.1634/theoncologist.12-6-636. PMid:17602055.

5. Parinyanitikul N, Lei X, Chavez-Mac Gregor M, et al. Receptor status change from primary to residual breast cancer after neoadjuvant chemotherapy (NCT) and analysis of survival outcome. J Clin Oncol. 2013;31(Suppl 26):48. http://dx.doi.org/10.1200/jco.2013.31.26_suppl.48.

6. Niikura N, Tomotaki A, Miyata H, et al. Changes in tumor expression of HER2 and hormone receptors status after neoadjuvant chemotherapy in 21 755 patients from the Japanese breast cancer registry. Ann Oncol. 2016;27(3):480-7. http://dx.doi.org/10.1093/annonc/mdv611. PMid:26704052.

7. Broom RJ, Tang PA, Simmons C, et al. Changes in Estrogen Receptor, Progesterone Receptor and Her-2/neu Status with Time: Discordance Rates Between Primary and Metastatic Breast Cancer. Anticancer Res. 2009;29(5):1557-62. PMid:19443366.

8. Fisher R, Pusztai L, Swanton C. Cancer heterogeneity: implications for targeted therapeutics. Br J Cancer. 2013;108(3):479-85. http://dx.doi.org/10.1038/bjc.2012.581. PMid:23299535.

9. Lohse I, Borgida A, Cao P, et al. BRCA1 and BRCA2 mutations sensitize to chemotherapy in patient-derived pancreatic cancer xenografts. Br J Cancer. 2015;113(3):425-32. http://dx.doi.org/10.1038/bjc.2015.220. PMid:26180923.

10. Birkbak NJ, Eklund AC, Li Q, et al. Paradoxical Relationship between Chromosomal Instability and Survival Outcome in Cancer. Cancer Res. 2011;71(10):3447-52. http://dx.doi.org/10.1158/0008-5472.CAN-10-3667. PMid:21270108.

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