Taxanes for the treatment of breast cancer during pregnancy: an international cohort study.

INTRODUCTION: The addition of taxanes to anthracycline-based chemotherapy is considered standard of care in the treatment of breast cancer. However, there are insufficient data regarding the safety of taxanes during pregnancy. The aim of this study was to describe the incidence of obstetric and neonatal adverse events associated with the use of taxane-containing chemotherapy regimens for the treatment of breast cancer during pregnancy. METHODS: This is a multicenter, international cohort study of breast cancer patients treated with taxanes during pregnancy. A descriptive analysis was undertaken to synthetize available data. RESULTS: A total of 103 patients were included, most of whom were treated with paclitaxel and anthracyclines given in sequence during gestation (90.1%). The median gestational age at taxane initiation was 28 weeks (range = 12-37 weeks). Grade 3-4 adverse events were reported in 7 of 103 (6.8%) patients. The most common reported obstetric complications were intrauterine growth restriction (n = 8 of 94, 8.5%) and preterm premature rupture of membranes (n = 5 of 94, 5.3%). The live birth rate was 92 of 94 (97.9%), and the median gestational age at delivery was 37 weeks (range = 32-40 weeks). Admission to an intensive care unit was reported in 14 of 88 (15.9%) neonates, and 17 of 70 (24.3%) live births resulted in small for gestational age neonates. Congenital malformations were reported in 2 of 93 (2.2%). CONCLUSION: Obstetric and neonatal outcomes after taxane exposure during pregnancy were generally favorable and did not seem to differ from those reported in the literature with standard anthracycline-based regimens. This study supports the use of taxanes during gestation when clinically indicated.

Contraception and Hormone Replacement Therapy in Healthy Carriers of Germline BRCA1/2 Genes Pathogenic Variants: Results from an Italian Survey.

Several myths and misconceptions exist about hormones in women with familial predisposition to cancer, and there are few real-life data on their prescription and uptake. To better understand how they are prescribed and accepted in healthy carriers of a BRCA1/2 pathogenetic variant, an online survey was uploaded on Google Forms and shared through social media closed groups of patients' associations, aBRCAcadabra and ACTO Campania. A total of 241 questionnaires were collected. Sexual quality of life was considered of the utmost importance by most of the respondents (mean score of 7 ± 2.8/10), but they felt the counseling they received by healthcare professionals on the topic was insufficient (4.9 ± 3.2/10). Only 57 women out of 233 (24.5%) had used hormonal contraception after being diagnosed as carriers of a BRCA pathogenetic variant, and 42 out of 148 (28.4%) underwent menopause hormonal therapy. The majority of women (53.6% for contraception and 61.5% for menopause) reported being dissatisfied with the counseling received, and 58.2% were not aware of the protective effect of hormonal contraception on the risk of ovarian cancer. An educational effort is desirable to guarantee healthy BRCA carriers reliable contraception and evidence-based menopause counseling.

Early Breast Cancers During Pregnancy Treated With Breast-Conserving Surgery in the First Trimester of Gestation: A Feasibility Study.

Breast cancer is the most common malignancy occurring during gestation. In early-stage breast cancer during pregnancy (PrBC), breast-conserving surgery (BCS) with delayed RT is a rational alternative to mastectomy, for long considered the standard-of-care. Regrettably, no specific guidelines on the surgical management of these patients are available. In this study, we investigated the feasibility and safety of BCS during the first trimester of pregnancy in women with early-stage PrBC. All patients with a diagnosis of PrBC during the first trimester of pregnancy jointly managed in two PrBC-specialized Centers were included in this study. All patients underwent BCS followed by adjuvant radiotherapy to the ipsilateral breast after delivery. Histopathological features and biomarkers were first profiled on pre-surgical biopsies. The primary outcome was the isolated local recurrence (ILR). Among 168 PrBC patients, 67 (39.9%) were diagnosed during the first trimester of gestation. Of these, 30 patients (age range, 23-43 years; median=36 years; gestational age, 2-12 weeks; median=7 weeks; median follow-up time=6.5 years) met the inclusion criteria. The patients that were subjected to radical surgery (n=14) served as controls. None of the patients experienced perioperative surgical complications. No ILR were observed within three months (n=30), 1 year (n=27), and 5 years (n=18) after surgery. Among the study group, 4 (12.3%) patients experienced ILR or new carcinomas after 6-13 years, the same number (n=4) had metastatic dissemination after 3-7 years. These patients are still alive and disease-free after 14-17 years of follow-up. The rate of recurrences and metastasis in the controls were not significantly different. The findings provide evidence that BCS in the first trimester PrBC is feasible and reasonably safe for both the mother and the baby.

Reproductive issues in carriers of germline pathogenic variants in the BRCA1/2 genes: an expert meeting.

BACKGROUND: Healthy individuals and patients with cancer who are carriers of germline pathogenic variants in the BRCA1/2 genes face multiple reproductive challenges that require appropriate counseling and specific expertise. MAIN BODY: On December 5th-7th, 2019, patient advocates and physicians with expertise in the field of reproductive medicine, fertility preservation, and oncology were invited to "San Giuseppe Moscati" Hospital in Avellino (Italy) for a workshop on reproductive management of women with germline pathogenic variants in the BRCA1/2 genes. From the discussion regarding the current evidence and future prospective in the field, eight main research questions were formulated and eight recommendations were developed regarding fertility, fertility preservation, preimplantation genetic testing, and pregnancy in healthy carriers and patients with cancer. CONCLUSION: Several misconceptions about the topic persist among health care providers and patients often resulting in a discontinuous and suboptimal management. With the aim to offer patient-tailored counseling about reproductive issues, both awareness of current evidences and research should be promoted.

Ovarian transposition in patients with cervical cancer prior to pelvic radiotherapy: a systematic review.

Ovarian transposition aims to minimize ovarian exposure and damage during pelvic radiotherapy. One or both ovaries are separated from the uterus and mobilized away from the area where the radiation will be administered. A review of the available literature was conducted to evaluate the efficacy and safety of ovarian transposition among pre-menopausal women diagnosed with cervical cancer and eligible for pelvic radiotherapy. Outcomes evaluated were ovarian function preservation and complication rates. We also searched for information on pregnancy/live birth rates after ovarian transposition. Our search yielded a total of 635 manuscripts, of which 33 were considered eligible. A total of 28 full texts were selected for the current review, including 1377 patients who underwent ovarian transposition. The median or mean follow-up ranged between 7 and 87 months. Ovarian function preservation after ovarian transposition and pelvic radiotherapy, with or without chemotherapy, was 61.7% (431/699 patients), ranging from 16.6% to 100%. A total of 12 studies reported on 117 complications, accounting for 8.5%. Ovarian metastases were described in 5 (0.4%). Data about fertility preservation after ovarian transposition are scarce and definitive conclusions cannot be drawn. Based on the available data, ovarian transposition could be performed on young patients with tumors smaller than 4 cm, and it should be avoided in those with bulky tumors. A risk/benefit assessment should be carefully evaluated by a multidisciplinary team, and the decision regarding ovarian transposition should be always guided by the values and informed preferences of the patient.

Discussing motherhood when the oncological prognosis is dire: ethical considerations for physicians.

Physicians are increasingly open to discussing and supporting pregnancy after cancer treatment. However, counselling patients who are seeking pregnancy despite advanced oncological disease and/or uncertain prognosis is still challenging. Two paradigmatic cases are presented and analysed to illustrate the ethical uneasiness faced by treating physicians when seriously ill patients seek fertility preservation and/or pregnancy. Review of ethical issues is built around the four principles of biomedical ethics. Respect for patients autonomy in relation to managing realistic expectations and avoiding giving patients false hopes opens the analysis. It is followed by considering fair allocation of resources and meaningful distinction between protecting patients from harm and contributing to their welfare. Responsibilities towards the unborn child are discussed in a light of maternal and fetal interdependency. Respecting personal autonomy requires abstaining from controlling inferences to the individual patient's choices, but it does not mean that patients should be left on their own to pick and choose their disease management approaches without advice and guidance from healthcare professionals. Physicians should reason evaluating the potential harms and checking if benefits will outweigh the risks and if costs will produce the best overall results. Responsibilities towards the unborn child can be managed by balancing the respect for maternal autonomy and beneficence for pregnant woman and her fetus. The oncologist cannot determine how patients should view their disease but with empathy and compassion can help them understand the logical rationale behind clinical advice.

First-in-human pharmacokinetics of tamoxifen and its metabolites in the milk of a lactating mother: a case study.

BackgroundBreast cancer represents the most frequent neoplasm diagnosed in women of childbearing age. When the tumour is oestrogen receptor-positive, tamoxifen is among the recommended endocrine treatments. Lactating women are advised not to breastfeed while receiving tamoxifen. However, information about tamoxifen transfer into breast milk is lacking.MethodsWe measured the concentration of tamoxifen and its metabolites by liquid chromatography-tandem mass spectrometry in the milk of a nursing mother that was treated for pregnancy-associated breast cancer diagnosed a few months after delivery. She was advised not to breastfeed her child and she collected milk samples for 23 days while the baby was fed with formula.ResultsTamoxifen concentrations in milk increased reaching a maximum of 214 nM. The two active metabolitesZ-4-hydroxy-tamoxifen and Z-endoxifen, could not be quantified in milk the first days after tamoxifen intake, but increased over time and reached clinically significant levels after day 18.ConclusionThis study demonstrates for the first time in human that tamoxifen and its metabolites transfer into milk. Since tamoxifen has a complete oral bioavailability, a long half-life (>7 days) and may interfere with the normal development of the infant, mothers should not breastfeed during tamoxifen treatment.

Fertility preservation in women with cervical cancer.

Fertility preservation in women with cervical cancer is a demanding but evolving issue. Some remarkable achievements have been reached, in particular the improvement of primary and secondary prevention and the broadening of the indications for conservative surgery up to FIGO 2018 stage IB2. Natural pregnancy rate and the rate of obstetrics complications following conservative approach is satisfactory even if not optimal. On the other hand, the use of classic strategies for fertility preservation such as oocytes or ovarian cortex freezing is extremely limited, being the uterus compromised by treatment in a high proportion of cases. In fact, the availability of uterine surrogacy can play a role in the counseling and the decision-making process. The recent advent of uterus transplantation is fascinating but, at present, cannot be viewed as a realistic solution.

Lactation during and after Breast Cancer.

Breastfeeding is an important aspect of mother-newborn relationship and is of great benefit for the baby. Unfortunately, many drugs taken by the mother may pass into her milk and exert an effect on the newborn. Very limited data is available and a cautionary approach is warranted especially when the woman receives anticancer treatment including chemotherapy , hormonal treatment and the recently introduced target agents as well as monoclonal antibodies. In all these conditions breastfeeding should be put on hold.More and more often physicians are faced with women that are pregnant years after the diagnosis of cancer: this has long been considered dangerous for the mother, but data show that prognosis is definitely not worse. If the woman is no longer being actively treated, breastfeeding is advisable every time it is possible, even if patients that received breast radiation may be unable to produce a sufficient amount of milk on that side.

Management of HER2-positive breast cancer during pregnancy: a case report.

INTRODUCTION: Breast cancer is one of the most common malignancies diagnosed during pregnancy, with an incidence of 1:3000 pregnancies. Its rising incidence is related to the trend to postpone childbearing during the last 30 years. Breast cancer during pregnancy should not be managed differently from the nonpregnant setting. Chemotherapy is reported to be safe after the first trimester, whereas trastuzumab and tamoxifen are contraindicated regardless of the trimester. CASE DESCRIPTION: A patient diagnosed with breast cancer recurrence during pregnancy was exposed to both tamoxifen and trastuzumab during the first two trimesters of pregnancy. In addition, docetaxel was administered during the second and third trimesters, without subsequent fetal malformations or obstetric complications. CONCLUSIONS: When conception occurs inadvertently during assumption of tamoxifen or anti-HER2 agents, their effects on the fetus and on the course of pregnancy are not completely understood. Further studies are needed in this setting, highlighting the importance to share clinical experiences.

Tamoxifen Exposure during Pregnancy: A Systematic Review and Three More Cases.

Tamoxifen is frequently used as adjuvant treatment in premenopausal patients with hormone receptor-positive early breast cancer. According to guidelines, the use of nonhormonal barrier contraception is recommended during tamoxifen treatment and up to 3 months after its interruption prior to attempting conception. Nevertheless, when conception occurs inadvertently during tamoxifen treatment, the effects on the fetus and on the course of pregnancy are still not completely known. Here, we report 3 cases of young women who accidentally became pregnant while taking tamoxifen and perform a systematic review of the literature to provide more elements for better and clear multidisciplinary counselling of women facing this challenging situation.

Uterine irradiation as a determinant of infertility and pregnancy losses in young cancer survivors.

Several concerns exist regarding the impact of anticancer treatments on fertility and pregnancy outcome. The detrimental effects of both chemotherapy and radiotherapy on the ovaries are well reported in the available literature. Fewer data are focused on the importance of a functioning uterus to conceive and carry on a healthy pregnancy. The aim of this paper is to provide a narrative review of the current literature to assess the role of uterine irradiation as a potential determinant of infertility and poor obstetrical outcomes. This review addresses the need for multidisciplinary counselling in order to face the poor reproductive and obstetrical outcomes of women who had uterine radiation, according to the different backgrounds (radiotherapy during adulthood versus childhood; total body irradiation versus pituitary, spinal and/or abdominal-pelvic irradiation).

Frequency of Pregnancy-Associated Cancer: A Systematic Review of Population-Based Studies.

Despite numerous available resources of evidence, the results about the frequency of pregnancy-associated cancer (PAC) still show poor comparability due to dissimilarities in the study design and methodology, inclusion criteria, incoherent duration of follow-up and a heterogeneous reference population. We conducted a systematic review of population-based studies on PAC published up to December 2019, to provide updated research on this topic, highlighting strengths and limitations. Of the 24 papers included, 11 considered all types of tumors and 13 dealt with specific types of cancer. Differences in the procedures for estimating the frequency of PAC emerged even among population studies. However, we found consistent results for overall frequency of PAC- around 1/1000 pregnancies. Our review suggests that about 25% of PAC cases are diagnosed during pregnancy, confirming the hypothesis of an excess of diagnosis in the postpregnancy period. Sparse and inconsistent results were found regarding a potential increase in the frequency of PAC over calendar years. Alignments in the strategy to identify PAC are needed to overcome methodological weaknesses.

Can we trust tumour markers in pregnancy after breast cancer? A case of elevated CA 15-3 in the third trimester of pregnancy normalising after delivery.

We realized a narrative review of the current literature starting from the case of a patient with raised CA15-3 during an uncomplicated pregnancy after breast cancer. The aim of our paper was to assess specificity, physiological changes and clinical utility of CA 15-3 monitoring during pregnancy after breast cancer, starting from clinical practice and retrieving the most relevant evidence in the literature.