Risk factors for the increasing incidence of pregnancy-associated cancer in Sweden - a population-based study.

INTRODUCTION: The incidence of cancer during pregnancy and within first year post-delivery, ie pregnancy-associated cancer (PAC), is increasing in many countries, but little is known about risk factors for these trends. This study quantified incidence of PAC by trimesters and post-delivery periods, and assessed the role of maternal age, parity, immigrant status, education, smoking and body mass index for the risk and incidence trends of PAC. MATERIAL AND METHODS: We used data from the national birth and cancer registers in Sweden during 1973-2017 to define a register-based cohort of women aged 15-44 years. Incidence rates of PAC during pregnancy and up to 1 year post-delivery were calculated per 100 000 deliveries per year. Poisson regression with multiple imputation estimated incidence rate ratios with 95% confidence intervals adjusted by year, age, previous parity, immigrant status, education, smoking and BMI during 1990-2017, when information on risk factors was available. RESULTS: Among 4 557 284 deliveries, a total of 1274 (during pregnancy) and 3355 (within 1 year post-delivery) cases of PAC were diagnosed, with around 50 cases/year diagnosed during pregnancy and 110 cases/year during the first year post-delivery in the latest period 2015-2017. The most common cancer types during pregnancy were malignant melanoma, breast and cervical cancer, together accounting for 57% of cases during pregnancy and 53% during the first year post-delivery. The numbers of PAC were lower during pregnancy than during post-delivery for all tumor types with lowest numbers during first trimester. The PAC incidence rates increased over calendar time. High maternal age at diagnosis, smoking, nulliparity and non-immigrant background were associated with significantly higher risks of PAC. The increasing PAC incidence was in part explained by higher maternal age over time, but not by the other factors. CONCLUSIONS: High maternal age is the strongest risk factor for PAC. We show for the first time that smoking, nulliparity and non-immigrant background are also contributing risk factors for PAC. However, only high maternal age contributed significantly to the increasing incidence. Further studies on other potential risk factors for PAC are warranted, since our results indicate that age on its own does not fully explain the increase.

Epidemiology of Pregnancy-Associated Breast Cancer.

Breast cancer diagnosed during pregnancy or lactation up to 1 year post-partum is often referred to as pregnancy-associated breast cancer (PABC) , although the definition varies with length of post-partum period. The incidence rate has been reported to range from 17.5 to 39.9 per 100,000 births, but the rate is substantially lower during pregnancy (ranging from 3.0 to 7.7) than during the post-partum period (ranging from 13.8 to 32.2). The PABC incidence rate is increasing in many populations, and higher maternal age at birth is a likely explanation. Linkable population-based data on pregnancies and cancer are required to obtain reliable estimates of PABC incidence. In studies comparing outcomes in women with PABC to other young breast cancer patients, it is crucial to adjust for age, since the age distribution of PABC depends both on age at pregnancy and age at breast cancer. Large studies have shown similar prognosis for women with PABC compared to other young women with breast cancer, when accounting for differences in age, stage and other tumour characteristics.

The Palliative Radiotherapy and Inflammation Study (PRAIS) - protocol for a longitudinal observational multicenter study on patients with cancer induced bone pain.

BACKGROUND: Radiation therapy (RT) results in pain relief for about 6 of 10 patients with cancer induced bone pain (CIBP) caused by bone metastases. The high number of non-responders, the long median time from RT to pain response and the risk of adverse effects, makes it important to determine predictors of treatment response. Clinical features such as cancer type, performance status and pain intensity, and biomarkers for osteoclast activity are proposed as predictors of response to RT. However, results are inconsistent and there is a need for better predictors of RT response. A similar argument can be stated for the development of cachexia; there are currently no predictors that can identify patients who will develop cachexia later in the cancer disease trajectory. Experimental and preclinical studies show that pain, depression and cachexia are related to inflammation. However, it is not known if inflammatory biomarkers can predict CIBP, depression or development of cachexia. METHODS: This multicenter, multinational longitudinal observational study will include 600 adult patients receiving RT for CIBP. Demographic data, clinical variables, osteoclast and inflammatory biomarkers will be assessed before start of RT, and 3, 8, 16, 24 and 52 weeks after last course of RT. The primary aim of the study is to identify potential predictors for pain relief from RT. Secondary aims are to explore potential predictors for development of cachexia, the longitudinal relationship between pain intensity and depression, and if inflammatory biomarkers are associated with changes in pain intensity, cachexia and depression during one-year follow up. DISCUSSION: The immediate clinical implication of the PRAIS study is to identify potential predictive factors for a RT response on CIBP, and thereby reduce non-efficacious RT. Patient benefits are fewer hospital visits, reduced risk of adverse effects and more individualized pain treatment. The long-term clinical implication of the PRAIS study is to improve the knowledge about inflammation in relation to CIBP, cachexia and depression and potentially identify associations and mechanisms that can be targeted for treatment. TRIAL REGISTRATION: ClinicalTrials.gov NCT02107664 , date of registration April 8, 2014 (retrospectively registered). TRIAL SPONSOR: The European Palliative Care Research Centre (PRC), Department of Clinical and Molecular Medicine, NTNU, Faculty of medicine and Health Sciences, Trondheim, N-7491, Norway.

Birth outcomes among offspring of adult cancer survivors: a population-based study.

Do cancer and cancer treatment influence patients' subsequent pregnancies and outcomes for the offspring? In this study, we compared birth outcomes in 3,915 female and male survivors and 144,653 controls from the general population with similar parity, by merging data from the Cancer Registry and the Medical Birth Registry of Norway. The cancer survivors were diagnosed at age 16-45 in the period 1967-2004. Subgroups of nulliparous survivors (childless before cancer) and primiparous (one pregnancy before and one after cancer) were analyzed, using logistic regression to compare birth outcomes with controls, focusing perinatal death, congenital anomalies, preterm birth (<37 gestational weeks) and low birth weight (LBW, <2,500 g). We adjusted for maternal age, birth period and educational level. Nulliparous female survivors' offspring had increased risk of preterm birth (OR = 1.30 [95% CI 1.05-1.61]) but similar risks of LBW and perinatal death as their controls. Primiparous female survivors differed from their controls, with higher frequency of preterm birth (OR = 1.89 [95% CI 1.40-2.56]) and LBW at term (OR = 2.02 [95% CI 1.15-3.55]). A borderline significant increase of perinatal death was seen among offspring of primiparous female survivors, with OR = 1.92 (95% CI 0.98-3.76). Offspring of male survivors did not differ from their controls. For all cancer types combined, no increased risk of congenital anomalies was seen among either female or male survivors' offspring. Pregnant female cancer survivors should be offered close follow-up, as there is an increased risk of adverse birth outcomes, in particular among those with higher parities.

Benefits of Study Participation for Patients with Advanced Cancer Receiving Radiotherapy: A Prospective Observational Study.

Background: Patients with advanced cancer and bone metastases may have unmet palliative care (PC) needs that go unnoticed during clinical oncological practice. This observational study describes interventions that were initiated as the patients participated in the Palliative Radiotherapy and Inflammation Study (PRAIS). It was hypothesized that the patients would benefit from study participation due to PC interventions initiated by the study team. Methods: A retrospective review of patients' electronic records. Patients with advanced cancer and painful bone metastases included in PRAIS were eligible. All patients met with the study team before start of radiotherapy, after completion of Patient Reported Outcome Measures. Interventions initiated by the study team were documented in the patients' electronic records. Results: A total of 133 patients were reviewed: 63% males, mean (standard deviation [SD]) age 65 (9.6) and mean (SD) Karnofsky performance status (KPS) score 73.2 (9.1). Interventions were initiated in 50% (n = 67) of the patients. Changes in opioid management (69%), treatment of constipation (43%), and nausea (24%) and nutritional advice were most frequent (21%). Patients receiving interventions had lower mean KPS (70 vs. 77 p < 0.001), shorter survival time after study inclusion (median 28 vs. 57.5 weeks p = 0.005) and were more often opioid naïve (12% vs. 39% p < 0.001) than those not receiving interventions by the study team. Conclusions: Patients with advanced cancer and painful bone metastasis benefited from study participation due to multiple PC interventions initiated by the study team. The findings call for a systematic integration of PC in patients with advanced cancer. Trial Registration: ClinicalTrials.gov NCT02107664.

Pregnancy after adolescent and adult cancer: a population-based matched cohort study.

Despite fertility-preserving initiatives, postcancer reproduction is expected to be lower than that of the general population. Using data from the Cancer Registry and the Medical Birth Registry of Norway, postcancer pregnancy rates were analyzed in 27,556 survivors and compared to those from a matched comparison group ("controls") from the general population. All were born after 1950, diagnosed from 1967 to 2004 at age of 16-45, and had an observation time from the date of diagnosis (assigned date for controls), until pregnancy, death, age 46, or December 31, 2006. Cox regression was used to estimate pregnancy rates, after adjusting for educational level, parity and diagnostic period. Overall, cancer survivors had a lower pregnancy rate than the controls, but the rate for survivors was higher in males than in females [hazard rate (HR)=0.74 (95% confidence interval (CI) 0.71-0.78) and HR=0.61 (95% CI 0.58-0.64), respectively]. However, the rates did not differ between controls and survivors of malignant melanoma or thyroid cancer. By contrast, the lowest HRs for pregnancy occurred in survivors of leukemia, cervical or breast cancer. Increased pregnancy rates during the study period were detected for ovarian cancer [HR=0.2 (95% CI 0.1-0.3) to HR=0.7 (95% CI 0.5-0.9)], testicular cancer [HR=0.6 (95% CI 0.4-0.9) to HR=0.8 (95% CI 0.7-0.8)], and Hodgkin lymphoma diagnosed in men [HR=0.7 (95% CI 0.5-0.9) to HR=0.9 (95% CI 0.7-1.0)]. In summary, fertility-preserving attempts have succeeded in patients with ovarian or testicular cancer and in males with Hodgkin lymphoma. Male survivors initiated pregnancies in a higher degree than female survivors.

Cancer survival in women diagnosed with pregnancy-associated cancer: An overview using nationwide registry data in Sweden 1970-2018.

BACKGROUND: Pregnancy-associated cancer (PAC) is increasing over time in many countries. We provide a comprehensive, population-based overview of cancer survival in women with PAC across five decades. METHODS: We performed a nationwide cohort study of 121,382 women diagnosed with cancer at age 15-49 between 1970 and 2018 using birth and cancer registers in Sweden. Pregnancy-associated cancer was defined as diagnosed during pregnancy and within one year of delivery, while non-PAC was outside this window. Cox regression estimated adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) comparing cancer mortality for PAC versus non-PAC. RESULTS: In total, 5079 women had a diagnosis of PAC. Cutaneous malignant melanoma, breast, cervical, thyroid and central nervous system (CNS) were the most common sites of PAC. A higher cancer mortality was observed in PAC versus non-PAC for breast (HR = 1.72, 95% CI 1.54-1.93) and uterine cancer (myometrium/unspecified) (8.62, 2.80-26.53), in which all PAC deaths were uterine sarcomas. Increased mortality was also observed in upper digestive tract cancer diagnosed during pregnancy and colon cancer diagnosed during first year after delivery. Contrary, the HR for CNS tumours was significantly decreased (0.71, 0.55-0.91). Survival after PAC improved for most sites over time, with survival after breast cancer during pregnancy in recent years being similar to that of non-pregnancy associated breast cancer. CONCLUSION: For the majority of sites, PAC was not associated with poorer prognosis compared to non-PAC, a finding which was stable over time. The main exceptions were breast cancer and rarer cancers, such as uterine sarcoma.

Breast carcinoma in pregnancy with spheroid-like placental metastases-a case report.

Breast cancer is one of the most common malignancies diagnosed in pregnancy. Although the tumor is often detected at an advanced stage, placental metastases are rare. Here, we describe the case of a woman with breast cancer recurrence during pregnancy and subsequent metastases. The focus of this study is the large amount of placenta metastases, which have been analyzed immunohistochemically. Staining with trophoblast markers (placenta alkaline phosphatase, beta human chorionic gonadotropin and human placental lactogen) showed the strict localization of metastases in the intervillous space without invasion into fetal tissue. They have a large spheroidal shape and are free of blood vessels. Staining with Ki-67 revealed an outer proliferative shell and inner necrotic core. At week 28, a healthy newborn was born by elective cesarean section. A few weeks later, after surgery and FEC60 (fluorouracil, epirubicin, cyclophosphamide) cycles, the patient died. Breast cancer metastases in the placenta are rarely described. The special immunological environment in pregnancy may influence phenotype, growth, and behavior of tumor and metastases.

Breast Cancer Diagnosed During Pregnancy: Adapting Recent Advances in Breast Cancer Care for Pregnant Patients.

Breast cancer during pregnancy (BCP), although rare, is becoming more common and treatment should be as similar as possible to that for nonpregnant young patients with breast cancer. A group of specialists convened to review current guidelines and provide guidance on how recent advances in breast cancer diagnosis and treatment can be adapted for pregnant patients. The majority of patients with BCP will be considered for treatment during the pregnancy. Premature delivery should be avoided whenever possible. Most treatments, including sentinel lymph node biopsy, systemic therapy with taxanes, platinum agents, or dose-dense treatment can be safely given during pregnancy, after careful risk/benefit assessment for mother and child. Chemotherapy is contraindicated during the first trimester because of a higher risk of fetal malformations but is feasible in the second and third trimesters. Other treatments such as radiation therapy or anti-human epidermal growth receptor 2 treatment are in general not indicated during pregnancy but might be considered in some instances. Patient data should be collected in a systematic way whenever possible.

Cause-specific survival for women diagnosed with cancer during pregnancy or lactation: a registry-based cohort study.

PURPOSE: To assess if cancers diagnosed during pregnancy or lactation are associated with increased risk of cause-specific death. PATIENTS AND METHODS: In this population-based cohort study using data from the Cancer Registry and the Medical Birth Registry of Norway, 42,511 women, age 16 to 49 years and diagnosed with cancer from 1967 to 2002, were eligible. They were grouped as not pregnant (reference), pregnant, or lactating at diagnosis. Cause-specific survival for all sites combined, and for the most frequent malignancies, was investigated using a Cox proportional hazards model. An additional analysis with time-dependent covariates was performed for comparison of women with and without a postcancer pregnancy. The multivariate analyses were adjusted for age at diagnosis, extent of disease, and diagnostic periods. RESULTS: For all sites combined, no intergroup differences in cause-specific death were seen, with hazard ratio (HR) of 1.03 (95% CI, 0.86 to 1.22) and HR 1.02 (95% CI, 0.86 to 1.22) for the pregnant and lactating groups, respectively. Patients with breast (HR, 1.95; 95% CI, 1.36 to 2.78) and ovarian cancer (HR, 2.23; 95% CI, 1.05 to 4.73) diagnosed during lactation had an increased risk of cause-specific death. Diagnosis of malignant melanoma during pregnancy slightly increased this risk. For all sites combined, the risk of cause-specific death was significantly decreased for women who had postcancer pregnancies. CONCLUSION: In general, the diagnosis of most cancer types during pregnancy or lactation does not increase the risk of cause-specific death. Breast and ovarian cancer diagnosed during lactation represents an exception. We confirmed the "healthy mother effect" for women with a postcancer pregnancy.