Katalin Ormándi

Tumor Topoisomerase II Alpha Status and Response to Anthracycline-Based Neoadjuvant Chemotherapy in Breast Cancer

Objectives: Individualized chemotherapy for breast cancer improves the outcome. Anthracyclines target the enzyme topoisomerase IIα (TOP2A). We set out to perform a retrospective study of the presence of gene abnormalities and the expression of TOP2A in a cohort of breast cancer patients treated with neoadjuvant anthracycline-based chemotherapy. Methods: Forty-three patients with 45 breast cancers were treated with neoadjuvant docetaxel-epirubicin with/without capecitabine chemotherapy. The TOP2A status of the cancers, determined retrospectively by fluorescent in situ hybridization and immunohistochemistry, was analyzed in relation to the standard clinical and pathological data. Results: Clinically and pathologically complete remission (pCR) was achieved in 15 (33.3%) and 9 (20%) cases, respectively. The TOP2A gene was amplified in 2 human epidermal growth factor receptor 2 (HER2)-positive cancers (8%), and 32 (84.2%) overall exhibited TOP2A expression in >15% of the cells. The expression of TOP2A exhibited a strong correlation with the expression of Ki67 (R = 0.743, p < 0.001), and was negatively correlated with estrogen receptors (ER; R = 0.404, p = 0.012) and progesterone receptors (R = 0.430, p = 0.007). The expression of TOP2A was not related to the amplification of the TOP2A gene or the HER2 status of the tumor. The proportions of Ki67- and TOP2A-positive tumor cells were significantly reduced after chemotherapy (56.1 ± 23.6 vs. 19.0 ± 27.7%, p = 0.004, and 41.0 ± 27.9 vs. 12.7 ± 24.8%, p < 0.001, respectively). The development of pCR was related to a high grade (p = 0.054), ER negativity (p = 0.027) and high TOP2A expression (p = 0.037). The expression of TOP2A was an independent predictor of pCR (OR = 1.460, for every 10% increase, 95% CI: 1.016–2.096, p = 0.041). After a median follow-up time of 31.0 months, neither relapse-free survival nor overall survival was related to the tumor response. Conclusions: TOP2A expression is a marker of the tumor’s proliferation rate and sensitivity to anthracycline-based chemotherapy, and does not depend on the amplification of its gene.

Az örökletes emlőrák szűrésének, megelőzésének és kezelésének új nemzetközi irányvonalai – hazai vonatkozásokkal

Absztrakt Bevezetes: Az orokletes emlőrak szűrese, megelőzese es kezelese osszetett, multidiszciplinaris feladat. A familiaris emlőrak ellatasara uj ajanlasokat publikaltak az Egyesult Kiralysagban. Celkitűzes: A szerzők az angliai es skociai ajanlasokat, azok evidenciait es az ezzel kapcsolatos magyarorszagi helyzetet foglaljak ossze. Modszer: A National Institute for Health and Care Excellence es a Familial Breast Cancer Report (NHS Scotland) ajanlasai es a hazai gyakorlat elemzese. Eredmenyek: Az uj ajanlasok jelentősen novelik a genetikai tesztek es az ezzel kapcsolatos genetikai tanacsadasok szamat. Az uj ajanlasok alapjan lenyegesen tobb magneses rezonancias vizsgalat javasolt az emlőszűresben. Az erintett egyeneknek kozepes kockazattol felfele kemoprevencio ajanlhato. Az orokletes emlőrak szisztemas kezeleseben uj utakat nyithatnak az egyes platinaszarmazekokkal es a poli-ADP-riboz polimeraz inhibitorokkal vegzett klinikai vizsgalatok. Az egeszsegugyi koltsegvetest szamottevően megterhelhetik a jel...INTRODUCTION Screening, prevention and treatment of familial breast cancer require a multidisciplinary approach. New guidelines were published in the United Kingdom for the management of familial breast cancer. AIM The authors summarise these new guidelines and analyse the relevant practice in Hungary. METHOD Relevant guidelines of the National Institute for Health and Care Excellence and Familial Breast Cancer Report (NHS Scotland) are described. RESULTS New guidelines will increase the number of genetic tests as well as genetic counselling. An increase in the number of breast magnetic resonance imaging is expected, too. Chemoprevention can be offered for individuals with medium risk and above. Promising trials are underway with platinum based chemotherapy and polyADP-ribose polimerase inhibitors for the systemic treatment of familial breast cancer. The increase in the number of genetic tests, counselling, and breast magnetic resonance imaging may have a significant impact on health care budget. CONCLUSIONS These guidelines will change some aspects of the current management of familial breast cancer. Orv. Hetil., 2016, 157(28), 1117-1125.

Long-Term Efficiency and Toxicity of Adjuvant Dose-Dense Sequential Adriamycin-Paclitaxel-Cyclophosphamide Chemotherapy in High-Risk Breast Cancer

Objectives: To perform a protocol-specified analysis of the dose-dense adriamycin-paclitaxel-cyclophosphamide (ddATC) study. Methods: Survival and late toxicity were analyzed in 55 patients enrolled to receive 4 × adriamycin 60 mg/m2, 4 × paclitaxel 200 mg/m2, 4 × cyclophosphamide 800 mg/m2, every 2 weeks, with cardioxane and filgrastim support. Kaplan-Meier curves were used to analyze relapse-free survival (RFS), distant disease-free survival (DDFS), and overall survival (OS). Survival analyses were performed according to the presence of casting-type calcifications on the mammogram. Results: After a median follow-up time of 78.5 (64.3–100.0) months, 29 (52.7%) patients were free of relapse (local, regional, distant or contralateral breast cancer), 34 (61.8%) patients were free of distant metastases, and 36 patients (65.5%) survived. The median times of RFS, DDFS and OS were not yet reached at 100.0 months. The median RFS, DDFS and OS times among breast cancer patients with tumors not associated with casting-type calcifications were >100.0 months, the corresponding parameters among patients with tumors accompanied by casting calcifications were 11.5 (p < 0.001), 11.5 (p < 0.001) and 29.6 months (p = 0.035), respectively. None of the patients developed myelodysplastic syndrome or leukemia. No cardiac failure occurred during the follow-up period. Conclusions: Our results indicate that adjuvant sequential ddATC is an efficient and less toxic chemotherapy regimen in high-risk breast cancer. The presence of casting-type calcifications on the mammogram points to a special biologic nature with very poor prognosis.