RESUMO
When ovarian stimulation is unfeasible, in vitro maturation (IVM) represents an alternative option for fertility preservation (FP). This retrospective study aims to evaluate the feasibility of performing within a short time frame two IVM cycles for FP. Seventeen women with breast cancer, 18-40 years of age, having undergone 2 cycles of IVM followed by oocyte vitrification were included. Non parametric analyses were used. No difference was observed between IVM1 and IVM2 outcomes. No complication was reported. The respective contributions of IVM1 and IVM2 for the number of cryopreserved oocytes were comparable irrespective of the delay between both procedures, even when performed during the same menstrual cycle. Those findings suggest that repeating IVM cycles may constitute a safe option for increasing the number of vitrified mature oocytes for FP. These two retrievals may be performed during the same cycle, providing additional argument for a physiologic continuous recruitment during follicular development.
Assuntos
Criopreservação/métodos , Preservação da Fertilidade/métodos , Infertilidade Feminina/fisiopatologia , Recuperação de Oócitos/métodos , Oócitos/fisiologia , Adulto , Neoplasias da Mama/fisiopatologia , Feminino , Humanos , Técnicas de Maturação in Vitro de Oócitos/métodos , Indução da Ovulação/métodos , Estudos Retrospectivos , Vitrificação , Adulto JovemRESUMO
Immunosurveillance plays an important role in breast cancer (BC) prognosis and progression, and can be geared by immunogenic chemotherapy. In a cohort of 1023 BC patients treated with neoadjuvant chemotherapy (NAC), 40% of the individuals took comedications mostly linked to aging and comorbidities. We systematically analyzed the off-target effects of 1178 concurrent comedications (classified according to the Anatomical Therapeutic Chemical (ATC) Classification System) on the density of tumor-infiltrating lymphocytes (TILs) and pathological complete responses (pCR). At level 1 of the ATC system, the main anatomical classes of drugs were those targeting the nervous system (class N, 39.1%), cardiovascular disorders (class C, 26.6%), alimentary and metabolism (class A, 16.9%), or hormonal preparations (class H, 6.5%). At level 2, the most frequent therapeutic classes were psycholeptics (N05), analgesics (N02), and psychoanaleptics (N06). Pre-NAC TIL density in triple-negative BC (TNBC) was influenced by medications from class H, N, and A, while TIL density in HER2+ BC was associated with the use of class C. Psycholeptics (N05) and agents acting on the renin-angiotensin system (C09) were independently associated with pCR in the whole population of BC or TNBC, and in HER2-positive BC, respectively. Importantly, level 3 hypnotics (N05C) alone were able to reduce tumor growth in BC bearing mice and increased the anti-cancer activity of cyclophosphamide in a T cell-dependent manner. These findings prompt for further exploration of drugs interactions in cancer, and for prospective drug-repositioning strategies to improve the efficacy of NAC in BC.
Assuntos
Terapia Neoadjuvante , Neoplasias de Mama Triplo Negativas , Animais , Humanos , Linfócitos do Interstício Tumoral , Camundongos , Estudos Prospectivos , Receptor ErbB-2 , Neoplasias de Mama Triplo Negativas/tratamento farmacológicoRESUMO
The role of gonadotropins in the genesis of malignant diseases, in particular gynecologic cancers, is still controversial. The production of ovarian steroids, as a consequence of FSH and LH actions, may constitute a bias to draw reliable conclusions. Over the past decades, the use of exogenous gonadotropins has markedly increased in cancer patients, candidates for fertility preservation, and in survivors facing infertility as a consequence of gonadotoxic treatments. In gynecologic cancers, high serum estradiol levels may be problematic and can therefore be overcome by specific protocols of ovarian stimulation. However, exogenous gonadotropin administration in cancer patients should systematically be included in a multidisciplinary approach. The present article discusses the possible role of gonadotropins as tumorigenic factors and the use of exogenous gonadotropins in females suffering from cancer.
Assuntos
Preservação da Fertilidade/métodos , Neoplasias dos Genitais Femininos/etiologia , Gonadotropinas/efeitos adversos , Gonadotropinas/fisiologia , Adulto , Animais , Modelos Animais de Doenças , Feminino , Hormônio Foliculoestimulante/fisiologia , Hormônio Liberador de Gonadotropina/análogos & derivados , Hormônio Liberador de Gonadotropina/metabolismo , Hormônio Liberador de Gonadotropina/uso terapêutico , Humanos , Infertilidade Feminina/tratamento farmacológico , Infertilidade Feminina/etiologia , Hormônio Luteinizante/fisiologia , Neoplasias/etiologia , Indução da Ovulação/efeitos adversos , Indução da Ovulação/métodos , Receptores do FSH/metabolismoRESUMO
Fertility preservation has become the second major objective in association with the remission, in young patients suffering from breast cancer. Patients should be referred for oncofertility counseling, as soon as possible after the diagnosis. A multidisciplinary approach, involving oncologists, reproductive endocrinologists and embryologists will allow an optimal strategy according to patients' age, the ovarian reserve and the cancer treatments. The field of fertility preservation is improving and offers more and more flexible techniques. Oocyte vitrification is no more considered experimental. Ovarian stimulation combining exogenous FSH and aromatase inhibitors may be the optimal strategy of fertility preservation, while maintaining physiologic serum estradiol levels. In vitro maturation of oocyte may offer an interesting option, possibly in combination with ovarian tissue cryopreservation, in case of neo-adjuvant chemotherapy. All these techniques should not be considered only as a frozen hope but should be part of the treatment of young patients.