Final analysis of the ALTTO trial:adjuvant trastuzumab in sequence or in combination with lapatinib in patients with HER2-positive early breast cancer [BIG 2-06/NCCTG N063D (Alliance)]

BACKGROUND: Dual anti-human epidermal growth factor receptor 2 (HER2) blockade has improved the outcomes of patients with early and metastatic HER2-positive breast cancer. Here we present the final 10-year analysis of the ALTTO trial.PATIENTS AND METHODS: The ALTTO trial (NCT00490139) is a prospective randomized, phase III, open-label, multicenter study that investigated the role of adjuvant chemotherapy and trastuzumab alone, in combination or sequentially with lapatinib. The primary endpoint was disease-free survival (DFS) and secondary endpoints included overall survival (OS), time to distant recurrence and safety.RESULTS: Overall, 6281 patients with HER2-positive early breast cancer were included in the final efficacy analysis in three treatment groups: trastuzumab (T), lapatinib + trastuzumab (L + T) and trastuzumab followed by lapatinib (T→L). Baseline characteristics were well balanced between groups. At a median follow-up of 9.8 years, the addition of lapatinib to trastuzumab and chemotherapy did not significantly improve DFS nor OS. The 10-year DFS was 77% in T, 79% in L + T and 79% in T→L, and the 10-year OS was 87%, 89% and 89%, respectively. The incidence of any cardiac event was low and similar in the three treatment groups.CONCLUSIONS: With a longer follow-up, no significant improvement was observed in DFS in patients treated with dual anti-HER2 blockade with lapatinib + trastuzumab compared to trastuzumab alone. The 10-year survival rates for the combination group are consistent with other studies that have explored dual anti-HER2 therapy.</p

Surgical treatment of primary breast cancer in the neoadjuvant setting

Abstract Background Neoadjuvant chemotherapy (NACT) is a standard treatment option for primary operable breast cancer when adjuvant chemotherapy is indicated. Methods This article reviews the use of NACT in breast cancer treatment. Results Pathological complete response (pCR) rates of up to 60 per cent have been reached for certain breast cancer subgroups. Patients achieving a pCR have a lower locoregional recurrence rate. Nevertheless, the rate of breast-conserving surgery seems to be stable at around 65–70 per cent, although more than 80 per cent of patients respond to NACT. The risk of local relapse does not appear to be higher after NACT, which supports the recommendation to operate within the new margins, as long as there is no tumour in the inked area of the surgical specimen. However, tumours do not shrink concentrically and the re-excision rate is higher after NACT. Mastectomy rates for lobular carcinomas remain high irrespective of tumour response. The role of sentinel lymph node biopsy (SLNB) in the context of NACT has been studied in recent years, and it is not yet completely clear which type of axillary staging is the most suitable. SLNB before NACT in clinically node-negative patients has been the preferred option. However, this practice is currently changing, and it seems advisable to have the SLNB after NACT to reduce the risk of a false-negative SLNB. Conclusion Overall, patients do benefit from NACT, especially those with human epidermal growth factor receptor 2-positive and triple-negative breast cancer, but surgical/local procedures need to be adapted. </jats:sec

Geschwindigkeit des Depressionsbeginns

ZusammenfassungGegenstand und Ziel: Depressive Episoden können schnell oder über Wochen langsam einschleichend beginnen. Dieses bedeutsame Merkmal affektiver Störungen ist bis jetzt kaum systematisch untersucht. Wir analysierten die Geschwindigkeit des Beginns depressiver Episoden bei Patienten mit einer unipolaren Depression (UD) und einer Depression im Rahmen einer bipolaren affektiven Störung (BD). Material und Methoden: Untersucht wurden 151 Patienten (UD: n = 108; BD: n = 43) mit dem strukturierten “Onset-of-Depression Inventory”. Patienten mit kritischen Lebensereignissen in den zwei Wochen vor Beginn der depressiven Symptomatik oder einem Switch von Manie in Depression wurden ausgeschlossen. Ergebnisse: Bei Patienten mit BD begann die depressive Episode signifikant schneller (58% &lt; 1 Woche; Median: &gt; 3 bis 7 Tage) als bei Patienten mit UD (7,4% &lt; 1 Woche; Median: &gt; 1 bis 4 Monate) (p &lt; 0,001). Schlussfolgerungen: Der schnelle Beginn depressiver Episoden innerhalb einer Woche ist typisch für bipolare, nicht aber für unipolare affektive Störungen. Klinische Relevanz: Der Beginn innerhalb einer Woche spricht für das Vorliegen einer BD und ist für eine UD, wenn keine akuten Auslöser vorliegen, untypisch.</jats:p