Second malignancies after breast cancer: the impact of different treatment modalities

Abstract

Treatment for non-metastatic breast cancer (BC) may be the cause of second malignancies in long-term survivors. Our aim was to investigate whether survivors present a higher risk of malignancy than the general population according to treatment received. We analysed data for 16 705 BC survivors treated at the Curie Institute (1981 -1997) by either chemotherapy (various regimens), radiotherapy (high-energy photons from a 60 Co unit or linear accelerator) and/or hormone therapy (2 -5 years of tamoxifen). We calculated age-standardized incidence ratios (SIRs) for each malignancy, using data for the general French population from five regional registries. At a median follow-up 10.5 years, 709 patients had developed a second malignancy. The greatest increases in risk were for leukaemia (SIR: 2.07 (1.52 -2.75)), ovarian cancer (SIR: 1.6 (1.27 -2.04)) and gynaecological (cervical/endometrial) cancer (SIR: 1.6 (1.34 -1.89); Po0.0001). The SIR for gastrointestinal cancer, the most common malignancy, was 0.82 (0.70 -0.95; Po0.007). The increase in leukaemia was most strongly related to chemotherapy and that in gynaecological cancers to hormone therapy. Radiotherapy alone also had a significant, although lesser, effect on leukaemia and gynaecological cancer incidence. The increased risk of sarcomas and lung cancer was attributed to radiotherapy. No increased risk was observed for malignant melanoma, lymphoma, genitourinary, thyroid or head and neck cancer. There is a significantly increased risk of several kinds of second malignancy in women treated for BC, compared with the general population. This increase may be related to adjuvant treatment in some cases. However, the absolute risk is small. The overall survival rate of patients with early advanced breast cancer (BC) has increased over the years largely because adjuvant therapy, whether chemotherapy, radiotherapy or hormone therapy, has helped prevent local and distant failures (Fox, 1979;Jones and Raghavan, 1993; EBCTCG, 2005). Second malignancies that occur in long-term survivors may be due to sporadic cancers that would have occurred anyway, environmental or genetic factors (Klijn et al, 1997;Schrag et al, 1997;Turner et al, 1999;Meijers-Heijboer et al, 2000;Pierce et al, 2000Pierce et al, , 2003 StoppaLyonnet et al, 2000;Galper et al, 2002;Kauff et al, 2002;Pierce, 2002;Robson, 2002;Seynaeve et al, 2004; Kirova et al, 2005aKirova et al, , b, 2006aLaki et al, 2007), or BC treatment (Neugut et al, 1993;Inskip et al, 1994;Ahsan and Neugut, 1998;Karlsson et al, 1998;Kirova et al, 1998 Kirova et al, , 2005aKirova et al, , b, 2007Obedian et al, 2000;Rubino et al, 2000;Scholl et al, 2001;Shousha et al 2001;Yap et al, 2002 Yap et al, , 2005Deutsch et al, 2003;Zablotska and Neugut, 2003;Zablotska et al, 2005;Mellemkjaer et al, 2006) The aim of this study was to estimate the risk of a second malignancy after adjuvant treatment for BC in a homogeneous cohort of patients from a single institution. The observed incidence of second malignancies in these BC patients was com...

Is the breast-conserving treatment with radiotherapy appropriate in BRCA1/2 mutation carriers? Long-term results and review of the literature

“…We and other authors demonstrated that the recurrence rate in BRCA1/BRCA2 carriers is not increased in this population of patients [28][29][30][31][32]. On the contrary, it is well known that after long latent period, the radiation therapy for breast cancer can induce malignant tumours after a latency of several years [33,34]. The risk of second cancers in this population of patients is insufficiently documented [35,36].…”

Antiestrogen Therapy for Breast Cancer Modifies the Risk of Subsequent Cutaneous Melanoma

“…These findings have been attributed to shared lifestyle and genetic risk factors, carcinogenic effect of treatment (in particular radiotherapy), and most commonly to better medical surveillance of women with previous breast cancer. Most of those studies addressing melanoma risk after breast cancer concerned patients treated in the distant past and therefore with treatment regimens not including hormonal therapy (15,16), or lacked antiestrogen data or when available, did not evaluate if hormonal therapy influenced melanoma risk (17,19,(20)(21)(22)24). To our knowledge, only 2 prior studies evaluated melanoma cancer risk among breast cancer patients according to hormonal therapy (23,24).…”

Cancers primitifs multiples de la thyroïde et du côlon : à propos d’un cas et revue de littérature

“…Le cancer thyroïdien (CT) peut être associé à des cancers primitifs de nombreux organes différents, notamment le cancer du sein [20][21][22], les hémopathies malignes [23], le cancer de l'oesophage [24], les cancers de la tête et du cou [25], le cancer du rein, de la prostate, de l'ovaire [26], les cancers du cerveau, du système nerveux central [27] et le cancer colorectal.…”