Breast cancer is one of the most common malignant tumors that threaten women’s health, and its incidence is increasing and the population is getting younger. Approximately 2% of patients are between the ages of 20 and 34, and 11% are between the ages of 35 and 44. Thanks to advances in treatment, despite the high incidence of breast cancer, the survival time frame of breast cancer patients is increasing, and the fertility of breast cancer patients is receiving more and more attention from healthcare professionals and patients. The safety of pregnancy in breast cancer patients has been controversial because adjuvant therapy can have a negative impact on the reproductive function of the patient. Whether these negative effects will adversely affect the survival and health status of the fetus, whether the discontinuation of estrogen resistance antagonists during pregnancy in estrogen receptor-positive patients will have negative effects on the survival of breast cancer patients, and whether pregnancy will increase the probability of breast cancer recurrence; these issues have not been uniformly discussed. (1) Effect of adjuvant therapy on reproductive function (1) Effect of chemotherapy on reproductive function Tissue cells that are actively regenerating are more sensitive to cytotoxic drugs, and the ovaries are always in a cyclic regenerative state, so they are vulnerable to damage by chemotherapy drugs. The effect of chemotherapy on ovarian function is related to the patient’s age, chemotherapy drug type, protocol, and dose. Cyclophosphamide has the most damaging effect on ovarian function, and some studies have shown that the number of follicles will decrease by 90% after 48 hours of application of cyclophosphamide, and ovarian function will diminish to the state of 10 years after 12-16 weeks of application of standard chemotherapy regimen. Anthracyclines and paclitaxel also have significant damage to ovarian function, and the probability of premature ovarian failure after chemotherapy has been reported abroad to be 29-93% for anthracycline-based drugs and 17-93% for paclitaxel plus anthracyclines. A research study involving 368 Asians showed that premature ovarian failure occurred in 83.6% of patients receiving chemotherapy; the majority were older than 40 years old, and 28 of 61 patients who developed premature ovarian failure subsequently resumed menstruation. The extent of ovarian damage from chemotherapy is influenced by the patient’s own follicular stores; younger patients with large follicular stores are generally less prone to permanent amenorrhea, and Fomier et al. found that the probability of long-term amenorrhea was around 15% in a follow-up of 166 patients aged less than 40 years [5]. Therefore, for young patients who have not yet had children at the time of diagnosis of breast cancer, patients should be informed that chemotherapy may lead to infertility, that follicular reserve assessment is required, and that pregnancy can be considered through other measures if the probability of premature ovarian failure is high, such as cryopreservation of oocytes, cryopreservation of embryos, cryopreservation of ovarian tissue, and use of gonadotropin-releasing hormone analogs (GnRHa) during chemotherapy. (2) Effects of endocrine therapy on fertility Most of the estrogen receptor positive patients with breast cancer need to receive endocrine therapy in the later stages, and premenopausal patients need to take oral tamoxifen treatment for at least 5 years. Tamoxifen inhibits ovulation, causes menstrual disorders, and may even increase the incidence of endometrial cancer; however, it is also believed that tamoxifen does not necessarily cause amenorrhea, as this may be a subsequent effect of prior chemotherapy received. Tamoxifen causing amenorrhea has been controversial. Most scholars believe that tamoxifen is less detrimental to ovarian function, but tamoxifen may cause fetal malformations, so patients treated with tamoxifen need to stop taking tamoxifen before pregnancy. (3) Effects of radiotherapy on reproductive function For patients with invasion of pectoralis major fascia, axillary lymph node metastasis or breast-conserving surgery, postoperative radiotherapy is required, but at present, radiotherapy for breast cancer is limited to chest irradiation, but a small amount of radiation can reach the pelvic cavity through muscle and blood. or more. Therefore, radiotherapy is safe for fertility, but radiotherapy may be detrimental to fetal health and pregnancy should be avoided during radiotherapy. For breast cancer patients who are mostly estrogen receptor positive, the question of whether the high hormone level in the patient’s body caused by pregnancy will have a negative impact on the patient’s prognosis has been controversial among scholars at home and abroad. Many scholars have conducted a series of retrospective investigations on this issue, with inconsistent results. Previous studies concluded that childbirth has no effect on survival in breast cancer patients, but the sample size was small. 2010 verkooijen et al. followed 492 treated pregnant and 8529 treated non-pregnant breast cancer patients and found that the mean follow-up time was 14.3 years and the overall mortality rate was at 16.8%, which was significantly lower than the overall mortality rate in treated non-pregnant patients (40.7%). Another meta-analysis of 14 case-control studies on the prognosis of patients who became pregnant after breast cancer treatment showed similar results. It was suggested that the possible reason for this result was the “healthy mother effect”. The healthy mother effect means that patients with a good early prognosis have a better chance of receiving a pregnancy, while patients with a poor late prognosis have a higher dose and course of chemotherapy, which is detrimental to reproductive function and is influenced by their disease and low expectation of post-treatment pregnancy. In order to eliminate this bias as much as possible, valachis et al. screened 20 relevant papers, excluding 11 of them with a more pronounced healthy maternal effect, and finally included an observation sample of 1097 and a control sample of 14224, concluding that pregnancy after treatment in breast cancer patients does not adversely affect patient survival. Since this study still did not absolutely exclude the healthy mother effect and was a retrospective investigation, lacking prospective studies, caution should be maintained regarding the idea that pregnancy after treatment in breast cancer patients improves survival. While following 333 breast cancer patients who became pregnant after treatment, Azim et al. divided the patients into two separate groups according to whether they were estrogen receptor positive or not and found that childbirth did not adversely affect the patients regardless of estrogen receptor positivity, which indirectly suggests that pregnancy does not have an improving effect on breast cancer prognosis [12]. In recent years the BRCK gene has become a hot topic in the field of breast cancer treatment, and for patients carrying the BRCA gene who may have lifelong disease, there is no evidence whether childbirth adversely affects the survival of such patients, and Valentini et al. followed 53 treated BRCA1 and BRCA2 gene carriers who became pregnant for a mean of 10.2 years and found that The birth of a child did not adversely affect their survival. Most breast cancer patients need to undergo postoperative radiotherapy and endocrine therapy, and many young breast cancer patients are afraid to give birth because of the concern of whether these treatments will have a negative impact on the health of the fetus. Theoretically, both radiotherapy and chemotherapy may cause chromosomal mutations that increase the probability of congenital malformations in the fetus, however, deBree,
However, a meta-analysis of six relevant papers by deBree, E et al. found that these adjuvant treatments did not increase the probability of fetal malformations, probably because primordial oocytes escape damage from chemotherapeutic agents, for example, and are renewed to mature oocytes after treatment. It has been shown that chemotherapy, even in mid- to late pregnancy, does not increase the probability of fetal malformations. de
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E et al. also found that four of the six papers did not mention more perinatal complications during childbirth in breast cancer patients, but two suggested that breast cancer patients may have perinatal complications such as miscarriage, preterm delivery, and relatively low birth weight of the fetus. The choice of timing of pregnancy is a concern for both clinicians and patients. For the sake of patient safety, most scholars believe that pregnancy should be avoided at the peak of breast cancer recurrence, i.e. 2-3 years after diagnosis.
A et al. concluded that pregnancy within 3 months of diagnosis significantly increases the relative risk of death in breast cancer patients, while pregnancy after 10 months of diagnosis decreases the relative risk of mortality to below normal values,
A et al. found that pregnancy in young breast cancer patients 6 months after completion of treatment did not reduce survival time. However, in hormone receptor-positive patients, pregnancy activity should be performed after completion of endocrine therapy because of the possible impact on survival due to the need to suspend tamoxifen during childbirth. For fetal safety reasons, pregnancy should also be carried out after 6 months after the end of treatment, when chemotherapeutic drugs are largely metabolized completely in the body. In conclusion, according to the available evidence, pregnancy activity in breast cancer patients does not reduce survival time and may be prognostically beneficial, but the appropriate timing should be chosen. Because the current studies are retrospective analyses of patients with early and intermediate stage breast cancer, there is no data on whether fertility is beneficial or detrimental to the prognosis of patients with advanced or recurrent metastases. Therefore, a cautious attitude should be maintained regarding fertility in this group of patients.