Asian Pacific Journal of Cancer Prevention

Asian Pacific Journal of Cancer Prevention (아시아태평양암예방학회)
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Molecular Types and Neoadjuvant Chemotherapy in Patients with Breast Cancer- While Molecular Shifting is More Common in Luminal a Tumors, The Pathologic Complete Response is Most Frequently Observed in Her-2 Like Tumors

  • Salim, Derya Kivrak (Department of Medical Oncology, Akdeniz University School of Medicine) ;
  • Mutlu, Hasan (Department of Medical Oncology, Akdeniz University School of Medicine) ;
  • Eryilmaz, Melek Karakurt (Department of Medical Oncology, Akdeniz University School of Medicine) ;
  • Musri, Fatma Yalcin (Department of Medical Oncology, Akdeniz University School of Medicine) ;
  • Tural, Deniz (Department of Medical Oncology, Akdeniz University School of Medicine) ;
  • Gunduz, Seyda (Department of Medical Oncology, Akdeniz University School of Medicine) ;
  • Coskun, Hasan Senol (Department of Medical Oncology, Akdeniz University School of Medicine)
  • Published : 2014.11.28
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Abstract

Background: Pathologic complete response (pCR) is one of the most important target end-points of neoadjuvant chemotherapy (NACT) in patients with breast cancer (BC). In present study, we aimed to investigate the relationship between molecular subtypes and NACT in patients with BC. Materials and Methods: Using the Akdeniz University database, 106 patients who received NACT for operable breast cancer were retrospectively identified. Prognostic factors before and after NACT were assessed. According to the molecular subtypes, molecular shifting after NACT and tumoral and nodal response to NACT were analyzed. Results: The distribution of subtypes was: Luminal A, 28.3% (n=30); Luminal B, 31.1% (n=33); HER2-like, 24.5% (n=26); and basal like/triple negative (BL/TN), 16.0% (n=17). According to molecular subtypes, pCR rates in both breast and axillary were 0%, 21.4%, 36.4% and 27.3% for luminal A, luminal B, HER2-like and BL/TN, respectively (p=0.018). Molecular subtype shifting was mostly seen in luminal A type (28.6%) after the NACT. The pCR rate in breast and axillary was significantly higher in patients with HER2-like type BC. Conclusions: In patients with HER-2 like type BC, NACT may be offered in early stages. Additionally, due to molecular shifting, adjuvant treatment schedule should be reviewed again, especially in the luminal A group.

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References

  1. Baselga J, Bradbury I, Eidtmann H, et al (2012). NeoALTTO Study Team. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet, 379, 633-40. https://doi.org/10.1016/S0140-6736(11)61847-3
  2. Carey LA, Perou CM, Livasy CA, et al (2006). Race, breast cancer subtypes, and survival in the carolina breast cancer study. JAMA, 295, 2492-502. https://doi.org/10.1001/jama.295.21.2492
  3. Carey LA, Dees EC, Sawyer L, et al (2007). The triple negative paradox: primary tumor chemosensitivity of breast cancer subtypes. Clin Cancer Res, 13, 2329-34. https://doi.org/10.1158/1078-0432.CCR-06-1109
  4. Carey LA (2013). Molecular intrinsic subtypes of breast cancer. In: UpToDate.
  5. Chuthapisith S, Permsapaya W, Warnnissorn M, et al (2012). Breast cancer subtypes identified by the ER, PR and HER-2 status in Thai women. Asian Pac J Cancer Prev, 13, 459-62. https://doi.org/10.7314/APJCP.2012.13.2.459
  6. Cortazar P, Zhang L, Untch M, et al (2014). Pathological complete response and long-term clinical benefit in breast cancer: the CTNeoBC pooled analysis. Lancet, 384, 164-72. https://doi.org/10.1016/S0140-6736(13)62422-8
  7. Edge S, Byrd DR, Compton CC, et al (2010). AJCC cancer staging manual (7th ed). New York, NY: Springer.
  8. Egwuonwu OA, Anyanwu SN, Nwofor AM (2013). Efficacy of neoadjuvant chemotherapy in down staging locally advanced pre-menopausal breast cancer in Eastern Nigeria: is four courses adequate? J Cancer Res Ther, 9, 638-43. https://doi.org/10.4103/0973-1482.126463
  9. Engstrom MJ, Opdahl S, Hagen AI, et al Molecular subtypes, histopathological grade and survival in a historic cohort of breast cancer patients. Breast Cancer Res Treat, 140, 463-73.
  10. Fan C, Oh DS, Wessels L, et al (2006). Concordance among gene-expression-based predictors for breast cancer. N Engl J Med, 355, 560-9 https://doi.org/10.1056/NEJMoa052933
  11. Ferlay J, Shin HR, Bray F etal. (2008). Estimates of worldwide burden of cancer in 2008: GLOBOCAN 2008. Int J Cancer, 127, 2893-917.
  12. Genestie C, Zafrani B, Asselain B, et al (1998). Comparison of the prognostic value of Scarff-Bloom-Richardson and Nottingham histological grades in series of 825 cases of breast cancer:major importance of the mitotic count as a component of both grading systems. Anticancer Res, 18, 571-6.
  13. Gianni L, Pienkowski T, Im YH, et al (2012). Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol, 13, 25-32. https://doi.org/10.1016/S1470-2045(11)70336-9
  14. Hu Z, Fan C, Oh DS, et al (2006). The molecular portraits of breast tumors are conserved across microarray platforms. BMC Genomics, 7, 96. https://doi.org/10.1186/1471-2164-7-96
  15. Irigoyen MA, Garcia FV, Iturriagagoitia AC, et al (2011). Molecular subtypes of breast cancer: prognostic implications and clinical and immunohistochemical characteristics. An Sist Sanit Navar, 34, 219-33. https://doi.org/10.4321/S1137-66272011000200008
  16. Kadivar M, Mafi N, Joulaee A, Shamshiri A, Hosseini N (2012). Breast cancer molecular subtypes and associations with clinicopathological characteristics in Iranian women, 2002-2011. Asian Pac J Cancer Prev, 13, 1881-6. https://doi.org/10.7314/APJCP.2012.13.5.1881
  17. Keramatinia A, Mousavi-Jarrahi SH, Hiteh M, Mosavi-Jarrahi A (2014). Trends in incidence of breast cancer among women under 40 in Asia. Asian Pac J Cancer Prev, 15, 1387-90. https://doi.org/10.7314/APJCP.2014.15.3.1387
  18. Khokher S, Qureshi MU, Mahmood S, Nagi AH (2013). Association of immunohistochemically defined molecular subtypes with clinical response to presurgical chemotherapy in patients with advanced breast cancer. Asian Pac J Cancer Prev, 14, 3223-8. https://doi.org/10.7314/APJCP.2013.14.5.3223
  19. Loi S, Haibe-Kains B, Desmedt C, et al (2007). Definition of clinically distinct molecular subtypes in estrogen receptor-positive breast carcinomas through genomic grade. J Clin Oncol, 25, 1239-46. https://doi.org/10.1200/JCO.2006.07.1522
  20. Lv M, Li B, Li Y, et al (2011). Predictive role of molecular subtypes in response to neoadjuvant chemotherapy in breast cancer patients in Northeast China. Asian Pac J Cancer Prev, 12, 2411-7.
  21. Najafi B, Anvari S, Roshan ZA (2013). Disease free survival among molecular subtypes of early stage breast cancer between 2001 and 2010 in Iran. Asian Pac J Cancer Prev, 14, 5811-6. https://doi.org/10.7314/APJCP.2013.14.10.5811
  22. Parker JS, Mullins M, Cheang MC, et al (2009). Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol, 27, 1160-7. https://doi.org/10.1200/JCO.2008.18.1370
  23. Potemski P, Kusinska R, Watala C, et al (2005). Prognostic relevance of basal cytokeratin expression in operable breast cancer. Oncology, 69, 478-85, https://doi.org/10.1159/000090986
  24. Prat A, Perou CM. (2011) Deconstructing the molecular portraits of breast cancer. Mol Oncol, 5, 5-23. https://doi.org/10.1016/j.molonc.2010.11.003
  25. Ruano R, Ramos M, Garcia-Talavera JR, et al (2014). Sentinel node biopsy after neoadjuvant chemotherapy in breast cancer. Its relation with molecular subtypes. [Article in Spanish]. Rev Esp Med Nucl Imagen Mol. doi: 10.1016/j. remn. 2014.04.003. [Epub ahead of print]
  26. Schnitt SJ (2010). Classification and prognosis of invasive breast cancer: from morphology to molecular taxonomy. Mod Pathol, 23, 60-4. https://doi.org/10.1038/modpathol.2010.33
  27. Untch M, Fasching PA, Konecny GE, et al (2011). Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol, 29, 3351-7. https://doi.org/10.1200/JCO.2010.31.4930
  28. Untch M, Loibl S, Bischoff J, et al (2012). German Breast Group (GBG); Arbeitsgemeinschaft Gynakologische Onkologie-Breast (AGO-B) Study Group. Lapatinib versus trastuzumab in combination with neoadjuvant anthracycline-taxane-based chemotherapy (GeparQuinto, GBG 44): a randomised phase 3 trial. Lancet Oncol, 13, 135-44. https://doi.org/10.1016/S1470-2045(11)70397-7
  29. Valero V, Buzdar AU, Hortobagyi GN. (1996) Locally advanced breast cancer. Oncologist, 1, 8-17.
  30. Valero V, Buzdar AU, McNeese M, Singletary E, Hortobagyi GN (2003) Primary chemotherapy in the treatment of breast cancer: the University of Texas M. D. AndersonCancer Center experience. Clin Breast Cancer, 2, 63-8.
  31. Voduc KD, Cheang MC, Tyldesley Set al. (2010). Breast cancer subtypes and the risk of local and regional relapse. J Clin Oncol, 28, 1684-91 https://doi.org/10.1200/JCO.2009.24.9284
  32. von Minckwitz G, Untch M, Nuesch E, et al (2011). Impact of treatment characteristics on response of different breast cancer phenotypes: pooled analysis of the German neoadjuvant chemotherapy trials. Breast Cancer Res Treat, 125, 145-56. https://doi.org/10.1007/s10549-010-1228-x
  33. von Minckwitz G, Untch M, Blohmer JU, et al (2012). Definition and impact of pathologic complete response on prognosis after neoadjuvant chemotherapy in various intrinsic breast cancer subtypes. J Clin Oncol, 30, 1796-804. https://doi.org/10.1200/JCO.2011.38.8595
  34. Widodo I, Dwianingsih EK, Triningsih E, Utoro T, Soeripto (2014). Clinicopathological features of Indonesian breast cancers with different molecular subtypes. Asian Pac J Cancer Prev, 15, 6109-13. https://doi.org/10.7314/APJCP.2014.15.15.6109
  35. Wolmark N, Wang J, Mamounas E, Bryant J, Fisher B (2001). Preoperative chemotherapy in patients with operable breast cancer: nine-year results from National Surgical Adjuvant Breast and Bowel Project B-18. J Natl Cancer Inst Monogr, 30, 96-102.

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