Bevezetés: Az örökletes emlőrák szűrése, megelőzése és kezelése összetett, multidiszciplináris feladat. A familiáris emlőrák ellátására új ajánlásokat publikáltak az Egyesült Királyságban. Célkitűzés: A szerzők az angliai és skóciai ajánlásokat, azok evidenciáit és az ezzel kapcsolatos magyarországi helyzetet foglalják össze. Módszer: A National Institute for Health and Care Excellence és a Familial Breast Cancer Report (NHS Scotland) ajánlásai és a hazai gyakorlat elemzése. Eredmények: Az új ajánlások jelentősen növelik a genetikai tesztek és az ezzel kapcsolatos genetikai tanácsadások számát. Az új ajánlások alapján lényegesen több mágneses rezonanciás vizsgálat javasolt az emlőszűrésben. Az érintett egyéneknek közepes kockázattól felfelé kemoprevenció ajánlható. Az örökletes emlőrák szisztémás kezelésében új utakat nyithatnak az egyes platinaszármazékokkal és a poli-ADP-ribóz polimeráz inhibitorokkal végzett klinikai vizsgálatok. Az egészségügyi költségvetést számottevően megterhelhetik a jelentősen megnövekedett genetikai tesztvizsgálatok, a genetikai tanácsadások, az emlő mágneses rezonanciás vizsgálatai. Következtetések: A fenti ajánlások bizonyos területeken meg fogják változtatni a familiáris emlőrák ellátásának jelenlegi klinikai gyakorlatát. Orv. Hetil., 2016, 157(28), 1117–1125.
Familial breast cancer: classification, care and managing breast cancer and related risks in people with a family history of breast cancer (NICE guidelines [CG164]). National Institute for Health and Care Excellence. 2013. https://www.nice.org.uk/guidance/cg164
Familial Breast Cancer Report. Healthcare Improvement Scotland. 2014. http://www.healthcareimprovementscotland.org/our_work/cancer_care_improvement/programme_resources/familial_breast_cancer_report.aspx
Van Der Looij, M., Szabo, C. Besznyak, I., et al.: Prevalence of founder BRCA1 and BRCA2 mutations among breast and ovarian cancer patients in Hungary. Int. J. Cancer, 2000, 86(5), 737–740.
Antoniou, A. C., Cunningham, A. P., Peto, J., et al.: The BOADICEA model of genetic susceptibility to breast and ovarian cancers: updates and extensions. Br. J. Cancer, 2008, 98(8), 1457–1466.
Phillips, K. A., Milne, R. L., Rookus, M. A., et al.: Tamoxifen and risk of contralateral breast cancer for BRCA1 and BRCA2 mutation carriers. J. Clin. Oncol., 2013, 31(25), 3091–3099.
Lee, J. M., Ledermann, J. A., Kohn, E. C.: PARP Inhibitors for BRCA1/2 mutation-associated and BRCA-like malignancies. Ann. Oncol., 2014, 25(1), 32–40.
Evans, D. G., Lalloo, F., Hopwood, P., et al.: Surgical decisions made by 158 women with hereditary breast cancer aged <50 years. Eur. J. Surg. Oncol., 2005, 31(10), 1112–1128.
Robson, M. E., Bradbury, A. R., Arun, B., et al.: American Society of Clinical Oncology Policy Statement Update: Genetic and genomic testing for cancer susceptibility. J. Clin. Oncol., 2015, 33(31), 3660–3667.
Rosenberg, S. M., Ruddy, K. J., Tamimi, R. M., et al.: BRCA1 and BRCA2 mutation testing in young women with breast cancer. JAMA Oncol., 2016, 2(6), 730–736.
Orban, T. I., Olah, E.: Emerging roles of BRCA1 alternative splicing. Mol. Pathol., 2003, 56(4), 191–197.
Orban, T. I., Olah, E.: Expression profiles of BRCA1 splice variants in asynchronous and in G1/S synchronized tumor cell lines. Biochem. Biophys. Res. Commun., 2001, 280(1), 32–38.
Orban, T. I., Olah, E.: Purifying selection on silent sites – a constraint from splicing regulation? Trends Genet., 2001, 17(5), 252–253.
Rebbeck, T. R., Mitra, N., Wan, F., et al.: Association of type and location of BRCA1 and BRCA2 mutations with risk of breast and ovarian cancer. JAMA, 2015, 313(13), 1347–1361.
Bojesen, S. E., Pooley, K. A., Johnatty, S. E., et al.: Multiple independent variants at the TERT locus are associated with telomere length and risks of breast and ovarian cancer. Nat. Genet., 2013, 45(4), 371–384.
Olah, E.: Molecular cancer genetics in eastern and central Europe. Dis. Markers, 1999, 15(1–3), 75–77.
Andrieu, N., Goldgar, D. E., Easton, D. F., et al.: Pregnancies, breast-feeding, and breast cancer risk in the International BRCA1/2 Carrier Cohort Study (IBCCS). J. Natl. Cancer Inst., 2006, 98(8), 535–544.
Antoniou, A., Pharoah, P. D., Narod, S., et al.: Average risks of breast and ovarian cancer associated with BRCA1 or BRCA2 mutations detected in case series unselected for family history: a combined analysis of 22 studies. Am. J. Hum. Genet., 2003, 72(5), 1117–1130.
Ramus, S. J., Kote-Jarai, Z., Friedman, L. S., et al.: Analysis of BRCA1 and BRCA2 mutations in Hungarian families with breast or breast-ovarian cancer. Am. J. Hum. Genet., 1997, 60(5), 1242–1246.
Olah, E.: Hereditary neoplastic diseases (genetic predisposition and cancer syndromes). [Örökletes genetikai betegségek (genetikai hajlam és daganat szindrómák).] Orv. Hetil., 1999, 140(9), 451–466. [Hungarian]
Kriege, M., Brekelmans, C. T., Obdeijn, I. M., et al.: Factors affecting sensitivity and specificity of screening mammography and MRI in women with an inherited risk for breast cancer. Breast Cancer Res. Treat., 2006, 100(1), 109–119.
Leach, M. O., Boggis, C. R., Dixon, A. K., et al.: Screening with magnetic resonance imaging and mammography of a UK population at high familial risk of breast cancer: a prospective multicentre cohort study (MARIBS). Lancet, 2005, 365(9473), 1769–1778.
Rijnsburger, A. J., Obdeijn, I. M., Kaas, R., et al.: BRCA1-associated breast cancers present differently from BRCA2-associated and familial cases: long-term follow-up of the Dutch MRISC Screening Study. J. Clin. Oncol., 2010, 28(36), 5265–5273.
Kuhl, C. K., Schrading, S., Leutner, C. C., et al.: Mammography, breast ultrasound, and magnetic resonance imaging for surveillance of women at high familial risk for breast cancer. J. Clin. Oncol., 2005, 23(33), 8469–8476.
Forrai, G., Szabó, E., Ormándi, K., et al.: Use of imaging methods for up-to-date diagnosis and screening of breast cancer. [A képalkotó vizsgálómódszerek alkalmazása az emlődaganatok korszerű diagnosztikájában és szűrésében.] Magy. Onkol., 2010, 54(3), 211–216. [Hungarian]
Cuzick, J., Forbes, J. F., Sestak, I., et al.: Long-term results of tamoxifen prophylaxis for breast cancer – 96-month follow-up of the randomized IBIS-I trial. J. Natl. Cancer Inst., 2007, 99(4), 272–282.
Vogel, V. G., Costantino, J. P., Wickerham, D. L., et al.: Update of the National Surgical Adjuvant Breast and Bowel Project Study of Tamoxifen and Raloxifene (STAR) P-2 Trial: Preventing breast cancer. Cancer Prevent. Res. (Phila.), 2010, 3(6), 696–706.
Romics, L. Jr., Chew, B. K., Weiler-Mithoff, E., et al.: Ten-year follow-up of skin-sparing mastectomy followed by immediate breast reconstruction. Br. J. Surg., 2012, 99(6), 799–806.
Meijers-Heijboer, H., van Geel, B., van Putten, W. L., et al.: Breast cancer after prophylactic bilateral mastectomy in women with a BRCA1 or BRCA2 mutation. N. Engl. J. Med., 2001, 345(3), 159–164.
Evans, D. G., Barwell, J., Eccles, D. M., et al.: The Angelina Jolie effect: how high celebrity profile can have a major impact on provision of cancer related services. Breast Cancer Res., 2014, 16(5), 442.
Hopwood, P., Lee, A., Shenton, A., et al.: Clinical follow-up after bilateral risk reducing (‘prophylactic’) mastectomy: mental health and body image outcomes. Psychooncology, 2000, 9(6), 462–472.
Khan, J., Barrett, S., Forte, C., et al.: Oncoplastic breast conservation does not lead to a delay in the commencement of adjuvant chemotherapy in breast cancer patients. Eur. J. Surg. Oncol., 2013, 39(8), 887–891.
Mátrai, Z., Gulyás, G., Tóth, L., et al.: The place of skin-sparing mastectomy in oncoplastic breast surgery. [A bőrtakarékos mastectomia helye a modern onkoplasztikai emlősebésztben.] Magy. Onkol., 2011, 55(4), 252–267. [Hungarian]
Mátrai, Z., Gulyás, G., Tóth, L., et al.: Oncoplastic challenges in modern breast surgery. [A modern emlősebészet onkoplasztikai kihívásai.] Magy. Onkol., 2011, 55(1), 40–52. [Hungarian]
Lloyd, S. M., Watson, M., Oaker, G., et al.: Understanding the experience of prophylactic bilateral mastectomy: a qualitative study of ten women. Psychooncology, 2000, 9(6), 473–485.
Sonnenblick, A., de Azambuja, E., Azim, H. A. Jr., et al.: An update on PARP inhibitors – moving to the adjuvant setting. Nat. Rev. Clin. Oncol., 2015, 12(1), 27–41.
Lord, C. J., Ashworth, A.: Mechanisms of resistance to therapies targeting BRCA-mutant cancers. Nat. Med., 2013, 19(11), 1381–1388.
Weil, M. K., Chen, A. P.: PARP inhibitor treatment in ovarian and breast cancer. Curr. Problems Cancer, 2011, 35(1), 7–50.
Tutt, A., Robson, M., Garber, J. E., et al.: Oral poly(ADP-ribose) polymerase inhibitor olaparib in patients with BRCA1 or BRCA2 mutations and advanced breast cancer: a proof-of-concept trial. Lancet, 2010, 376(9737), 235–244.
Gelmon, K. A., Hirte, H. W., Robidoux, A., et al.: Can we define tumors that will respond to PARP inhibitors? A phase II correlative study of olaparib in advanced serous ovarian cancer and triple-negative breast cancer. J. Clin. Oncol., 2010, 28(15 Suppl.), Abstr. 3002.
Isakoff, S. J., Overmoyer, B., Tung, N. M., et al.: A phase II trial of the PARP inhibitor veliparib (ABT888) and temozolomide for metastatic breast cancer. J. Clin. Oncol., 2010, 28(15 Suppl.), Abstr. 1019.
Byrski, T., Huzarski, T., Dent, R., et al.: Pathologic complete response to neoadjuvant cisplatin in BRCA1-positive breast cancer patients. Breast Cancer Res. Treat., 2014, 147(2), 401–405.
Von Minckwitz, G., Schneeweiss, A., Loibl, S., et al.: Neoadjuvant carboplatin in patients with triple-negative and HER2-positive early breast cancer (GeparSixto; GBG 66): a randomised phase 2 trial. Lancet Oncol., 2014, 15(7), 747–756.
Tutt, A., Ellis, P., Kilburn, L., et al.: The TNT trial: A randomized phase III trial of carboplatin (C) compared with docetaxel (D) for patients with metastatic or recurrent locally advanced triple negative or BRCA1/2 breast cancer (CRUK/ 07/012). Cancer Res., 2015, 75(9 Suppl.), Abstr. S3–01.
Isakoff, S. J., Mayer, E. L., He, L., et al.: TBCRC009: A multicenter phase II clinical trial of platinum monotherapy with biomarker assessment in metastatic triple-negative breast cancer. J. Clin. Oncol., 2015, 33(17), 1902–1909.
Baselga, J., Gomez, P., Awada, A., et al.: The addition of cetuximab to cisplatin increases overall response rate (ORR) and progression-free survival (PFS) in metastatic triple-negative breast cancer (TNBC): results of a randomized phase II study (BALI-1). Ann. Oncol., 2010, 21(8S), Abstr. 2740.
Kocsis, J., Béres, E., Horváth, Zs.: Up-to-date treatment of metastatic breast cancer. [A metasztatikus emlőrák korszerű kezelése.] Klin. Onkol., 2015, 2(4), 223–229. [Hungarian]
Stover, D. G., Winer, E. P.: Tailoring adjuvant chemotherapy regimens for patients with triple negative breast cancer. Breast, 2015, 24(Suppl. 2), S132–S135.
Gnant, M., Thomssen, C., Harbeck, N.: St. Gallen/Vienna 2015: A brief summary of the consensus discussion. Breast Care (Basel), 2015, 10(2), 124–130.
Cardoso, F., Costa, A., Norton, L., et al.: ESO-ESMO 2nd international consensus guidelines for advanced breast cancer (ABC2). Breast, 2014, 23(5), 489–502.