Pregnancy following breast cancer using assisted reproduction and its effect on long-term outcome

Introduction and aimsWe have previously shown that pregnancy is safe following breast cancer, even in endocrine sensitive disease. Yet infertility remains common following systemic treatment. To date, no study has evaluated the safety of assisted reproductive technology (ART) after breast cancer treatment. In this study, we evaluated the impact of ART on pregnancy and long-term outcomes of young breast cancer survivors.MethodsThis is a multi-centre retrospective study in which women who were diagnosed with breast cancer between 2000 and 2009, and had a pregnancy following breast cancer diagnosis were eligible. Patients were divided into two groups according to whether ART following primary systemic therapy was performed to achieve pregnancy. We evaluated the association between ART use and clinic-pathological characteristics, pregnancy outcome and long-term breast cancer outcome.ResultsA total of 198 patients were evaluated; of whom 25 underwent ART. No significant differences in tumour characteristics were observed between both groups, except for histological grade 3 tumours, which were fewer in the ART group (36% versus 59%, p = 0.033). Around 90% of patients received primary adjuvant chemotherapy and more than 50% had an endocrine sensitive disease. Patients in the ART group were older at diagnosis (31.4 versus 33.7 years, p = 0.009), at conception (38 versus 35 years, p < 0.001), and experienced more miscarriages (23.5 versus 12.6%, p = 0.082). Full term pregnancies were achieved in 77% and 76% of the spontaneous and ART groups, respectively. Mean follow-up between conception and last follow-up was 63 and 50 months in the spontaneous and ART groups, respectively with no difference in breast cancer outcome observed between the two groups (p = 0.54).ConclusionPregnancy using ART in women with history of breast cancer is feasible and does not seem to be detrimental to cancer outcome. Larger studies are needed to further confirm this observation.     

Management of breast cancer in pregnancy

The concurrent diagnosis of breast cancer and pregnancy remains a challenging clinical situation. Ethical concerns regarding maternal and fetal well-being and potential risks and harms of treatment influence the clinical decision process. Ethical considerations of treatment initiation have emphasized the role of autonomy for the patient and the concept of beneficence and non-maleficence for patient and fetus. Limited prospective data are available to assist the physician and patient in making an informed decision. Recent data on diagnosis, evaluation, and management of pregnant patients with breast cancer have informed the development of international recommendations and guidelines for management of breast cancer during pregnancy. This article reviews the epidemiology, clinical presentation, diagnosis, therapy, and outcomes of breast cancer occurring concomitantly with pregnancy.     

Breast cancer during pregnancy

Opinion statement The concurrent diagnosis of breast cancer and pregnancy is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. Modified radical mastectomy, the preferred surgical option in women with breast cancer during pregnancy, can be accomplished with minimal fetal risk. Although breast-conserving surgery (lumpectomy or quadrantectomy) can be performed, the radiation therapy required to complete local therapy for the breast must be delayed until after delivery because of the risks associated with fetal exposure to radiation. Although much of the literature on the pharmacologic treatment of breast cancer during pregnancy is anecdotal, recently published data from our institution support the premise that breast cancer can be treated safely during the second and third trimesters of pregnancy with combination chemotherapy consisting of 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC). Therapeutic abortion does not appear to improve survival for the mother, but it may be an option if maternal health is jeopardized or fetal anomalies are seen or suspected.     

"I'm pregnant and I have breast cancer"

Pregnancy is infrequently complicated by the diagnosis of a concurrent breast cancer. This presents a particularly complicated clinical problem. The treatment of breast cancer in young women involves a number of difficult decisions regarding therapy. These decisions become even more complex when the concerns of the safety of an unborn child are added to the equation. For breast cancers diagnosed late in the third trimester, it is relatively straight forward to delay therapy until after delivery. For women diagnosed earlier in pregnancy, there are legitimate concerns that delays in therapy may adversely affect outcomes. While there are no randomized trials addressing the optimal treatment of women in this situation, there are case reports, case series, and cohort experiences that provide some insight. There are recommendations available from an international working group and from the National Comprehensive Cancer Network that address the treatment of women in this situation. There is general consensus that both surgery and chemotherapy are relatively safe after the first trimester of pregnancy. It is generally agreed that therapeutic radiation, if necessary, should be delayed until completion of pregnancy.     

Paclitaxel and cisplatin in the treatment of metastatic non-small-cell lung cancer during pregnancy

The concomitant occurrence of cancer during pregnancy is a rare event. The cancers most frequently detected during pregnancy are breast, cervical, melanoma, ovarian, leukaemia and lymphoma, however the diagnosis of lung cancer during pregnancy is particularly exceptional. In this case, we report on a pregnant woman who was diagnosed with non-small-cell lung cancer and received therapy with paclitaxel and cisplatin.     

Breast cancer in the very young patient: a multidisciplinary case presentation

A case is presented that exemplifies many issues and controversies in the diagnosis and treatment of breast cancer in the very young. This woman was 22 years of age at diagnosis; she initially underwent breast-conservation therapy and adjuvant chemotherapy, retained fertility, had a subsequent uncomplicated pregnancy and delivery, and 7 years later developed a local recurrence in the breast. The discussion addresses risk factors, diagnosis, and treatment of breast cancer in the young; the impact of treatment on fertility; implications regarding pregnancy, and the management of local recurrence after breast conservation.     

Carcinoma of the breast during pregnancy: a review and update on treatment options.

Gestational breast cancer is occurring with increasing incidence because more women are delaying childbirth into their thirties and forties. Although breast cancer during pregnancy or within the first year postpartum is occurring more often, there is still some confusion regarding its treatment. Although breast conservation therapy has evolved as the major treatment in breast cancer, it has been thought that pregnancy was a contraindication for this type of breast cancer therapy due to risks imposed on the fetus by chemotherapy and radiation. However, recent studies have shown that the use of chemotherapeutics during the second and third trimesters is possible. Also, if chemotherapy is initiated after a lumpectomy, radiation can be withheld until after the birth of the baby when the cancer is detected in the second or third trimester.     

Physical activity in a German breast cancer patient cohort: one-year trends and characteristics associated with change in activity level

BackgroundPhysical activity (PA) is increasingly discussed as concomitant therapy after breast cancer diagnosis and can add to the alleviation of therapy- and disease-related symptoms. The objectives of this study were to describe PA behaviour in the course of breast cancer and to identify factors associated with change in PA.Methods1,067 German postmenopausal breast cancer patients were asked about their PA behaviour before breast cancer diagnosis, during therapy and 1 year after surgery. MET-hours per week (MET = metabolic equivalent) were calculated based on quantitative information about walking, bicycling for transportation purposes and sports by multiplying the average hours per week spent at each activity with an individual intensity score. Factors associated with change in MET·h/week in the course of breast cancer were identified using multiple linear regression.ResultsMedian PA decreased significantly during therapy from 36 to 14 MET·h/week (p < .001). Patients treated with chemo- and/or radiotherapy had a stronger decline in PA compared to patients without adjuvant therapy or those treated only with hormones (adjusted β = −9.73 to −13.54). The presence of medical risk factors (β = −5.56) was also associated with a decrease of PA during therapy. In contrast, participation in rehabilitation (β = 7.62) was associated with an increase of PA after therapy.ConclusionIn the light of the drastic decline in PA during therapy, programs promoting PA seem obligatory for all breast cancer patients. Patients treated with chemo- and/or radiotherapy and those with medical risk factors should particularly be assisted in reaching recommended activity levels by targeted interventions during and after therapy.     

Diagnostic and treatment considerations when newly diagnosed breast cancer coincides with pregnancy: a case report and review of literature

Breast cancer is the most common malignancy associated with pregnancy and is a rare but well-recognized complication. It is hypothesized that as more women continue to delay childbearing, the incidence of breast cancer in pregnancy will increase. Because of the lack of clinical experience with breast cancer in the setting of pregnancy, given its relative infrequency, many patients and physicians believe the diagnosis puts the life of the mother at odds with that of the fetus, but available data suggest that termination of the pregnancy does not improve the outcome for pregnant women with breast cancer. Often diagnosis is delayed because neither patient nor physician suspects malignancy. This report presents a recent case of a young primigravid woman with a newly appreciated breast mass seen at Northwestern University Feinberg School of Medicine as a means of discussing diagnostic considerations, therapeutic options, and supportive care available to the practitioner when managing a pregnant patient with breast cancer.     

Breast cancer during pregnancy

The care of a pregnant breast cancer patient is a challenging clinical situation that historically has placed the welfare of the mother in conflict with that of the fetus. For the woman in this situation, the emotions usually associated with pregnancy can be overshadowed by the emotions aroused by a diagnosis of breast cancer and its subsequent treatment. The majority of published information on the management of breast cancer during pregnancy has consisted of retrospective chart reviews, case reports, and anecdotes. There is a paucity of published data from the prospective study of women who are pregnant at the time of their breast cancer diagnosis. This review will endeavor to address the diagnosis, staging, and subsequent treatment of breast cancer during pregnancy. The limited information available for this group of women on the outcomes of labor, delivery, and neonatal health will also be reviewed. This review will not specifically address pregnancy that occurs after diagnosis and subsequent treatment for breast cancer. However, some data, particularly those of an epidemiologic nature, address breast cancer diagnosed during pregnancy or within the year following delivery.     

Serum 25-hydroxyvitamin D at pregnancy and risk of breast cancer in a prospective study

BackgroundSeveral laboratory and epidemiological studies have inversely linked endogenous vitamin D and the risk of breast cancer. The acquisition of vitamin D over time on the relative risk (RR) of the disease development is not known. In a longitudinal study, we evaluated the association between vitamin D levels at pregnancy over time with the risk of breast cancer, and pregnancy-associated breast cancer.MethodThe risk for subsequent development of breast cancer associated with serum 25-hydroxyvitamin (25-OHD) levels was assessed for consecutive (1st and 2nd pregnancy) samples of 100 cases, with mean lag times (μ_t) of 7.4 and 4.6 years between sampling and the diagnosis, and matched (parity, age, year, season) controls. Pregnancy-associated breast cancer (PABC, 111 case–control pairs, μ_t = 1year) risk was also studied. Odds ratios (ORs) with 95% confidence intervals (CI) were calculated using the lowest quintile as the reference.ResultsSerum 25-OHD level was not associated with an increased risk neither at the 1st nor at the 2nd pregnancy samples (OR = 1.4, 95%CI 0.6–3.4; OR 1.4, 95%CI 0.7–2.8, respectively), but was associated with an increased risk of PABC (OR = 2.7, 95%CI 1.04–6.7).ConclusionGenerally, vitamin D may not be related to breast cancer risk but the increased PABC risk fits the association of vitamin D with the most aggressive cancers, and warrants caution with vitamin D supplementation during pregnancy.     

Overall survival from breast cancer in women pregnant or lactating at or after diagnosis

The effect of concurrent or subsequent pregnancy or lactation has been studied in women with breast cancer to determine if these variables influence prognosis. Information was collected from 382 women potentially capable of bearing children, aged less than 45 years, in the Auckland Breast Cancer Study Group data file, a consecutive series of women diagnosed with breast cancer from 1976 to 1985, with a median follow-up of 10.2 years. The prevalence of both pregnancy at diagnosis and lactation at diagnosis was 2.6%. The incidence of pregnancy subsequent to diagnosis was 3.9%. Women pregnant at the time of breast cancer diagnosis had significantly more advanced disease than non-pregnant patients, and there was a similar trend for women lactating at diagnosis. Overall survival in these women was poor compared with the non-pregnant and non-lactating groups; only 2 of 10 pregnant patients and 0 of 10 lactating patients survived more than 12 years. The adverse outcome for women lactating at diagnosis of their breast cancer persisted despite allowance for nodal status, tumour size and age. However, survival was similar between pregnant and non-pregnant patients when these variables were taken into account. No significant differences in survival were found between those women who had pregnancies subsequent to diagnosis of breast cancer and breast cancer patients who did not become pregnant. © 1996 Wiley-Liss, Inc.     

Pregnancy and breast cancer: epidemiology, treatment, and safety issues

The relationship between pregnancy and breast cancer is complex, and a paucity of available data further complicates decision-making for many women diagnosed with breast cancer during pregnancy or desiring to become pregnant after such a diagnosis. Treatment of breast cancer during pregnancy requires a multidisciplinary care team and careful consideration of the risk of the disease and gestational age of the fetus, in conjunction with the patient's preferences. Chemotherapy should be deferred beyond the first trimester. There is no evidence that pregnancy in a breast cancer survivor will decrease long-term survival; in fact, studies suggest a potential protective effect of pregnancy after breast cancer in terms of the risk of recurrence. However, the available studies are limited by substantial potential biases, and concerns remain for some women and their doctors about the risks of pregnancy after breast cancer. This article reviews what is known about the association between pregnancy and breast cancer, discusses treatment options for women diagnosed with the disease during pregnancy, and summarizes evidence regarding the safety of pregnancy after breast cancer.     

Breast cancer and pregnancy

Breast cancer occurring during pregnancy is a relatively rare clinical situation that may present many difficult medical and psychosocial problems. Its diagnosis is commonly delayed, largely related to breast changes which normally occur during pregnancy. When matched for age and stage of disease, patients with breast cancer during pregnancy have the same prognosis as nonpregnant patients; the disease stage at diagnosis is the most important predictor of survival. Breast cancer diagnosed during pregnancy should be treated according to the same principles applied in nonpregnant patients. Termination of pregnancy does not appear to improve survival and thus, decisions regarding termination of pregnancy should be based on the desires of the patient, along with the urgency for radiation or chemotherapy that could potentially be harmful to the fetus. Subsequent pregnancy following the diagnosis of breast cancer does not have a known detrimental effect on survival, although it is usually wise to discourage pregnancy for the first few years following the diagnosis of breast cancer.     

妊娠期乳腺癌9例的诊断和综合治疗

目的：研究妊娠期乳腺癌在诊断和手术、化疗、放疗综合治疗方面的特殊性。方法：1992年12月-1999年6月,法国巴黎第十二大学附属Henri Mondor医院放疗科收治9例妊娠期乳腺癌患者,其中3例诊断于妊娠期,6例诊断于分娩后1年内。5例行乳心保留治疗,4例改良根治术。所有病例行术后放疗。7例接受化疗。结果：9例钼靶摄片中7例和所有的5例超声检查提示肿瘤征象,诊断时总体病期晚,I、Ⅱ、Ⅲ期比例分别为11%、44%和44%。中位随访60月（9-89月）时,6例无病生存,3例在治疗结束后14月-48月出现局部复发或远处转移。结论：妊娠期乳腺癌诊断延误较为常见,对分娩后确诊的患者,应重视妊娠、哺乳期乳房体检和超声检查在鉴别诊断房肿块中的作用。治疗原则必须兼顾疾病的迫切性和胎儿的安全性。在可以及时开展化疗和放疗的综合治疗的前提下,乳房保留治疗在早期妊娠期乳腺癌中是可行的。     

1484 例腋淋巴结阴性乳腺癌患者预后的多因素 Cox 模型分析

目的对腋淋巴结阴性乳腺癌患者进行预后分析。方法选择２２个可能对腋淋巴结阴性乳腺癌患者预后产生影响的非重复特征性临床因素，通过计算机Ｃｏｘ多因素分析模型，利用累积生存率，对１４８４例手术切除的腋淋巴结阴性乳腺癌患者进行预后分析。结果在选取的２２个因素中，月经状况、妊娠次数、病期、合并妊娠或哺乳、肿瘤大小、内乳淋巴结、术后放疗、术后三苯氧胺辅助治疗是影响腋淋巴结阴性乳腺癌患者预后的独立预后因素（Ｐ＜０．０５）。结论用临床资料对腋淋巴结阴性乳腺癌患者进行预后分析，可发现部分高危人群。腋淋巴结阴性的乳腺癌患者术后不宜放疗或行卵巢切除，术后三苯氧胺辅助治疗不应仅局限于绝经后或雌激素受体阳性的患者。如何选择高危人群进行术后化疗，有待进一步研究。     

Place de l’association radiothérapie encéphalique et thérapies systémiques dans le traitement des métastases cérébrales d’un cancer du sein

The incidence of brain metastases from breast cancer is increasing with diagnosis and therapeutics progress, especially with systemic therapies. The occurrence of multiple brain metastases remains a delicate situation when surgery and stereotactic radiosurgery are not indicated, nor available. Treatment strategy is based on the patient's general condition and extracranial disease status. Whole brain radiation therapy remains the gold standard local treatment but its efficacy is limited with a median overall survival of 6 months. New strategies are needed for increasing survival and patients’ quality of life. Combining radiation therapy and chemotherapy has been a subject of interest. This article sums up the different radiotherapy plus concomitant systemic therapies combinations for the treatment of brain metastases from breast cancer.     

The effectiveness of treatment for breast cancer patients]

The study of late results of treatment in 1166 patients with breast cancer permitted to find the percentage of a 5-year survival to be equal to 55.58, 37.93% of patients survived for 10 years, 28.25% -- for 15 years. In the first stage a 5-year survival was 87.20%, while in the second and third -- 57.7% and 31.56% of patients survived for 5 years, accordingly. The modern methods of radiotherapy (radiosurgical method, interstitial gamma therapy with Au-198 granules, distance grammatherapy on the machine LUCH) enhanced the efficacy of therapeutic measures in patients with widespread breast cancer. A complex diagnosis -- cytology, non-contrast mammography and mathematical analysis by means of a computer contributes to recognition of early forms of breast cancer.     

Safety of pregnancy following breast cancer diagnosis: a meta-analysis of 14 studies

Background

Due to the rising trend of delaying pregnancy to later in life, more women are diagnosed with breast cancer before completing their families. Therefore, enquiry into the feasibility and safety of pregnancy following breast cancer diagnosis is on the rise. Available evidence suggests that women with a history of breast cancer are frequently advised against future conception for fear that pregnancy could adversely affect their breast cancer outcome. Hence, we conducted a meta-analysis to understand the effect of pregnancy on overall survival of women with a history of breast cancer.

Methods

Two of the authors independently performed a literature search up to September 2009 with no language restrictions. Eligible studies were published retrospective control-matched, population-based and hospital-based studies that have addressed the impact of pregnancy on the overall survival of women with history of breast cancer. Pooling of data was done using the random effect model. Unpublished statistics from three studies were obtained to perform further subgroup and sensitivity analyses. This included examining the effect of pregnancy according to age at diagnosis, healthy mother effect, type of study, nodal status and other parameters.

Results

Fourteen studies were included in this meta-analysis (1244 cases and 18,145 controls). Women who got pregnant following breast cancer diagnosis had a 41% reduced risk of death compared to women who did not get pregnant [PRR: 0.59 (90% confidence interval (CI): 0.50-0.70)]. This difference was seen irrespective of the type of the study and particularly in women with history of node-negative disease. In a subgroup analysis, we compared the outcome of women with history of breast cancer who became pregnant to breast cancer patients who did not get pregnant and were known to be free of relapse. In this analysis, we did not find significant differences in survival between either group [PRR: 0.85; 95% CI: 0.53-1.35].

Conclusions

This study confirms that pregnancy in women with history of breast cancer is safe and does not compromise their overall survival. Hence, breast cancer survivors should not be denied the opportunity of future conception.     

Breast Cancer and Fertility

OPINION STATEMENT: The increased availability of assisted reproductive technologies (ART) allows women with fertility issues to increase their chances of a successful pregnancy with the use of medications that, in some cases, increase circulating estrogens. There has been significant concern that the use of these medications will increase the risk of hormone-sensitive cancers such as breast, ovarian and uterine malignancies. Additionally, for those women who are diagnosed with a breast cancer during their reproductive years, this diagnosis can be particularly difficult as future fertility is a major concern for many young breast cancer survivors. With the current available data, there does not appear to be a statistically significant increase in the risk of developing breast cancer with ART, although several series suggest a potential possible related increase in borderline ovarian and uterine cancers. For breast cancer survivors, there does not appear to be an increased risk of death associated with subsequent pregnancies when compared with breast cancer patients who did not have subsequent pregnancies, although waiting at least 2?years after the diagnosis of breast cancer potentially may convey a protective effect. Therefore, when systemic therapy for breast cancer is recommended, early counseling and referral to a reproductive endocrinologist is warranted to provide optimal fertility preservation options. Further safety and outcomes studies are warranted for children.