Treatment of breast cancer during pregnancy: an observational study.
ABSTRACT Little is known about the treatment of breast cancer during pregnancy. We aimed to determine whether treatment for breast cancer during pregnancy is safe for both mother and child.
We recruited patients from seven European countries with a primary diagnosis of breast cancer during pregnancy; data were collected retrospectively if the patient was diagnosed before April, 2003 (when the registry began), or prospectively thereafter, irrespective of the outcome of pregnancy and the type and timing of treatment. The primary endpoint was fetal health for up to 4 weeks after delivery. The registry is ongoing. The study is registered with ClinicalTrials.gov, number NCT00196833.
From April, 2003, to December, 2011, 447 patients were registered, 413 of whom had early breast cancer. Median age was 33 years (range 22-51). At the time of diagnosis, median gestational age was 24 weeks (range 5-40). 197 (48%) of 413 women received chemotherapy during pregnancy with a median of four cycles (range one to eight). 178 received an anthracycline, 15 received cyclophosphamide, methotrexate, and fluorouracil, and 14 received a taxane. Birthweight was affected by chemotherapy exposure after adjustment for gestational age (p=0·018), but not by number of chemotherapy cycles (p=0·71). No statistical difference between the two groups was observed for premature deliveries before the 37th week of gestation. 40 (10%) of 386 infants had side-effects, malformations, or new-born complications; these events were more common in infants born before the 37th week of gestation than they were in infants born in the 37th week or later (31 [16%] of 191 infants vs nine [5%] of 195 infants; p=0·0002). In infants for whom maternal treatment was known, adverse events were more common in those who received chemotherapy in utero compared with those who were not exposed (31 [15%] of 203 vs seven [4%] of 170 infants; p=0·00045). Two infants died; both were exposed to chemotherapy and delivered prematurely, but both deaths were thought not to be related to treatment. Median disease-free survival for women with early breast cancer was 70·6 months (95% CI 62·1-105·5) in women starting chemotherapy during pregnancy and 94·4 months (lower 95% CI 64·4; upper 95% CI not yet reached) in women starting chemotherapy after delivery (unadjusted hazard ratio 1·13 [95% CI 0·76-1·69]; p=0·539).
Although our data show that infants exposed to chemotherapy in utero had a lower birthweight at gestational age than did those who were unexposed, and had more complications, these differences were not clinically significant and, since none of the infants was exposed to chemotherapy in the first trimester, were most likely related to premature delivery. Delay of cancer treatment did not significantly affect disease-free survival for mothers with early breast cancer. Because preterm birth was strongly associated with adverse events, a full-term delivery seems to be of paramount importance.
BANSS Foundation, Biedenkopf, Germany and the Belgian Cancer Plan, Ministry of Health, Belgium.
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ABSTRACT: BackgroundA select number of relatively rare metastatic malignancies comprising trophoblast tumours, the rare childhood cancers, germ cells tumours, leukemias and lymphomas have been routinely curable with chemotherapy for more than 30 years. However for the more common metastatic malignancies chemotherapy treatment frequently brings clinical benefits but cure is not expected. Clinically this clear divide in outcome between the tumour types can appear at odds with the classical theories of chemotherapy sensitivity and resistance that include rates of proliferation, genetic development of drug resistance and drug efflux pumps. We have looked at the clinical characteristics of the chemotherapy curable malignancies to see if they have any common factors that could explain this extreme differential sensitivity to chemotherapy.DiscussionIt has previously been noted how the onset of malignancy can leave malignant cells fixed with some key cellular functions remaining frozen at the point in development at which malignant transformation occurred. In the chemotherapy curable malignancies the onset of malignancy is in each case closely linked to one of the unique genetic events of; nuclear fusion for molar pregnancies, choriocarcinoma and placental site trophoblast tumours, gastrulation for the childhood cancers, meiosis for testicular cancer and ovarian germ cell tumours and VDJ rearrangement and somatic hypermutation for acute leukemia and lymphoma. These processes are all linked to natural periods of supra-physiological apoptotic potential and it appears that the malignant cells arising from them usually retain this heightened sensitivity to DNA damage. To investigate this hypothesis we have examined the natural history of the healthy cells during these processes and the chemotherapy sensitivity of malignancies arising before, during and after the events.SummaryTo add to the debate on chemotherapy resistance and sensitivity, we would argue that malignancies can be functionally divided into 2 groups. Firstly those that arise in cells with naturally heightened apoptotic potential as a result of their proximity to the unique genetic events, where the malignancies are generally chemotherapy curable and then the more common malignancies that arise in cells of standard apoptotic potential that are not curable with classical cytotoxic drugs.BMC Cancer 01/2015; 15(1):11. · 3.32 Impact Factor
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ABSTRACT: This study investigated the clinicopathologic characteristics and survival of women diagnosed with pregnancy-associated breast cancer (PABC) in Taiwan. PABC is defined as breast cancer diagnosed during pregnancy or within 1 year after obstetric delivery. Our sample of PABC patients (N = 26) included all patients diagnosed at a major medical center in northern Taiwan from 1984 through 2009. Among these patients, 15 were diagnosed during pregnancy and 11 were diagnosed within 1 year after delivery. The comparison group included 104 patients within the same age range as the PABC patients and diagnosed with breast cancer not associated with pregnancy from 2004 through 2009 at the same hospital. Patients' initiating treatment delayed, 5-year and 10-year overall survival were delineated by stratified Kaplan-Meier estimates. Patients' characteristics were associated with initiating treatment delayed was evaluated with multivariate proportional hazards modeling. Antepartum PABC patients were younger and had longer time between diagnosis and treatment initiation than postpartum PABC patients. The predictor of treatment delayed was including birth parity, cancer stage, and pregnancy. The PABC group had larger tumors, more advanced cancer stage, and tumors with less progesterone receptor than the comparison group. The antepartum PABC patients had higher mortality than postpartum PABC and comparison groups within 5 years after diagnosis. Based on these results, we confirmed that pregnant women with breast cancer were more likely to delay treatment. Therefore, we recommend that breast cancer screening should be integrated into the prenatal and postnatal routine visits for early detection of the women's breast problems.PLoS ONE 11/2014; 9(11):e111934. · 3.53 Impact Factor
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ABSTRACT: IntroductionThe incidence of breast cancer diagnosed during pregnancy is expected to increase as more women delay childbearing in the United States. Treatment of cancer in pregnant women requires prudent judgment to balance the benefit to the cancer patient and the risks to the fetus. Prospective data on the outcomes of children exposed to chemotherapy in utero are limited for the breast cancer population.Methods Between 1992 and 2010, 81 pregnant patients with breast cancer were treated in a single-arm, institutional review board-approved study with 5-fluorouracil, doxorubicin, and cyclophosphamide (FAC) in the adjuvant or neoadjuvant setting. Labor and delivery records were reviewed for each patient and neonate. In addition, the parents or guardians were surveyed regarding the health outcomes of the children exposed to chemotherapy in utero.ResultsIn total, 78% of the women (or next of kin) answered a follow-up survey. At a median age of seven years, most of the children exposed to chemotherapy in utero were growing normally without any significant exposure-related toxicity or health problems. Three children were born with congenital abnormalities: one each with Down syndrome, ureteral reflux, and clubfoot. The rate of congenital abnormalities in the cohort was similar to the national average of 3%.Conclusions During the second and third trimesters, pregnant women with breast cancer can be treated with FAC safely without concerns for serious complications or short-term health concerns for their offspring who are exposed to chemotherapy in utero. Continued long-term follow-up of the children in this cohort is required.Trial registrationClinicalTrials.gov Identifier: NCT00510367. Other Study ID numbers: ID01-193, NCI-2012-01578. Registration Date: 7/31/2007.Breast cancer research: BCR 12/2014; 16(6):3414. · 5.88 Impact Factor