Worse histopathology and prognosis in women with breast cancer diagnosed during the second trimester of pregnancy.

BACKGROUND: Evidence suggests that women with breast cancer diagnosed during pregnancy (PrBC) and within 2 years of delivery (PPBC) have similar survival compared to women diagnosed not near pregnancy if adjusted for stage and subtype. To investigate whether this is true for all subtypes and for both pregnancy and post-delivery periods, we examined clinicopathologic features and survival in women with breast cancer by trimesters and 6-month post-delivery intervals. MATERIALS AND METHODS: Women diagnosed with invasive breast cancer during 1992-2018 at ages 18-44 years were identified in the Swedish Cancer Register, with information on childbirths from the Swedish Multi-Generation Register and clinical data from Breast Cancer Quality Registers. Each woman with PrBC or PPBC was matched 1 : 2 by age and year to comparators diagnosed with breast cancer not near pregnancy. Distributions of stage, grade, and surrogate subtypes were compared. Adjusted hazard ratios (HRs) with 95% confidence intervals (CIs) for breast cancer mortality were estimated using Cox regression. RESULTS: We identified 1430 women with PrBC and PPBC (181 during pregnancy, 499 during the first and 750 during the second year after delivery). Compared to 2860 comparators, women with PrBC and PPBC in the first year after delivery had a significantly higher proportion of luminal human epidermal growth factor receptor 2 (HER2)-positive, HER2-positive and triple-negative tumours, and more advanced stage at diagnosis. After adjustment for age, year, parity, country of birth, hospital region, subtype, and stage, women diagnosed during the second trimester had a worse prognosis than matched comparators (HR 1.8, 95% CI: 1.0-3.2). CONCLUSIONS: Women diagnosed during pregnancy or within the first year after delivery have a worse prognosis than women diagnosed not near pregnancy due to adverse tumour biology and advanced stage at diagnosis. A worse prognosis for women diagnosed during the second trimester remained after multivariable adjustment, possibly reflecting difficulties to provide optimal treatment during ongoing pregnancy.

ESMO Expert Consensus Statements on the management of breast cancer during pregnancy (PrBC).

The management of breast cancer during pregnancy (PrBC) is a relatively rare indication and an area where no or little evidence is available since randomized controlled trials cannot be conducted. In general, advances related to breast cancer (BC) treatment outside pregnancy cannot always be translated to PrBC, because both the interests of the mother and of the unborn should be considered. Evidence remains limited and/or conflicting in some specific areas where the optimal approach remains controversial. In 2022, the European Society for Medical Oncology (ESMO) held a virtual consensus-building process on this topic to gain insights from a multidisciplinary group of experts and develop statements on controversial topics that cannot be adequately addressed in the current evidence-based ESMO Clinical Practice Guideline. The aim of this consensus-building process was to discuss controversial issues relating to the management of patients with PrBC. The virtual meeting included a multidisciplinary panel of 24 leading experts from 13 countries and was chaired by S. Loibl and F. Amant. All experts were allocated to one of four different working groups. Each working group covered a specific subject area with two chairs appointed: Planning, preparation and execution of the consensus process was conducted according to the ESMO standard operating procedures.

Recurrence and survival after standard versus oncoplastic breast-conserving surgery for breast cancer.

BACKGROUND: Oncoplastic techniques in breast-conserving surgery (BCS) are used increasingly for larger tumours. This large cohort study aimed to assess oncological outcomes after oncoplastic BCS (OPS) versus standard BCS. METHODS: Data for all women who had BCS in three centres in Stockholm during 2010-2016 were extracted from the Swedish National Breast Cancer Register. All patients with T2-3 tumours, all those receiving neoadjuvant treatment, and an additional random sample of women with T1 tumours were selected. Medical charts were reviewed for local recurrences and surgical technique according to the Hoffman-Wallwiener classification. Date and cause of death were retrieved from the Swedish Cause of Death Register. RESULTS: The final cohort of 4178 breast cancers in 4135 patients was categorized into three groups according to surgical technique: 3720 for standard BCS, 243 simple OPS, and 215 complex OPS. Median duration of follow up was 64 (range 24-110) months. Node-positive and large tumours were more common in OPS than in standard BCS (P < 0.001). There were 61 local recurrences: 57 (1.5 per cent), 1 (0.4 per cent) and 3 (1.4 per cent) in the standard BCS, simple OPS and complex OPS groups respectively (P = 0.368). Overall, 297 patients died, with an unadjusted 5-year overall survival rate of 94.7, 93.1 and 92.6 per cent respectively (P = 0.350). Some 102 deaths were from breast cancer, with unadjusted 5-year cancer-specific survival rates of 97.9, 98.3 and 95.0 per cent respectively (P = 0.056). DISCUSSION: Oncoplastic BCS is a safe surgical option, even for larger node-positive tumours, with low recurrence and excellent survival rates.

Gynecologic cancers in pregnancy: guidelines based on a third international consensus meeting.

We aimed to provide comprehensive protocols and promote effective management of pregnant women with gynecological cancers. New insights and more experience have been gained since the previous guidelines were published in 2014. Members of the International Network on Cancer, Infertility and Pregnancy (INCIP), in collaboration with other international experts, reviewed existing literature on their respective areas of expertise. Summaries were subsequently merged into a manuscript that served as a basis for discussion during the consensus meeting. Treatment of gynecological cancers during pregnancy is attainable if management is achieved by collaboration of a multidisciplinary team of health care providers. This allows further optimization of maternal treatment, while considering fetal development and providing psychological support and long-term follow-up of the infants. Nonionizing imaging procedures are preferred diagnostic procedures, but limited ionizing imaging methods can be allowed if indispensable for treatment plans. In contrast to other cancers, standard surgery for gynecological cancers often needs to be adapted according to cancer type and gestational age. Most standard regimens of chemotherapy can be administered after 14 weeks gestational age but are not recommended beyond 35 weeks. C-section is recommended for most cervical and vulvar cancers, whereas vaginal delivery is allowed in most ovarian cancers. Breast-feeding should be avoided with ongoing chemotherapeutic, endocrine or targeted treatment. More studies that focus on the long-term toxic effects of gynecologic cancer treatments are needed to provide a full understanding of their fetal impact. In particular, data on targeted therapies that are becoming standard of care in certain gynecological malignancies is still limited. Furthermore, more studies aimed at the definition of the exact prognosis of patients after antenatal cancer treatment are warranted. Participation in existing registries (www.cancerinpregnancy.org) and the creation of national tumor boards with multidisciplinary teams of care providers (supplementary Box S1, available at Annals of Oncology online) is encouraged.

What is the impact of chronic systemic inflammation such as rheumatoid arthritis on mortality following cancer?

BACKGROUND: Emerging evidence links inflammation and immune competence to cancer progression and outcome. Few studies addressing cancer survival in the context of rheumatoid arthritis (RA) have reported reduced survival without accounting for the underlying mortality risk in RA. Whether this increased mortality is a cancer-specific phenomenon, an effect of the decreased lifespan in RA or a combination of both remains unknown. METHODS: Using Swedish register data (2001-2009), we performed a cohort study of individuals with RA (N=34 930), matched to general population comparators (N=169 740), incident cancers (N=12 676) and deaths (N=14 291). Using stratified Cox models, we estimated HRs of death associated with RA in the presence and absence of cancer, by stage and time since cancer diagnosis, for all cancers and specific sites. RESULTS: In the absence of cancer, RA was associated with a doubled mortality rate (HR=2.1, 95% CI 2.0 to 2.2). In the presence of cancer, the relative effect of RA on mortality was varied by stage. For cancer (tumour, node, metastases) stages I and II at diagnosis, the relative effect of RA on mortality was the same as in the absence of cancer. For cancers diagnosed at advanced stages with absolute higher mortality, the effect decreased (HR=1.2, 95% CI 1.1 to 1.3). These associations remained across time since cancer diagnosis and were reasonably similar across cancer sites. CONCLUSIONS: Much of the increase in mortality in patients with RA diagnosed with cancer seems to reside with effects of RA independently of the cancer.

Time-dependent risk of developing distant metastasis in breast cancer patients according to treatment, age and tumour characteristics.

BACKGROUND: Metastatic breast cancer is a severe condition without curative treatment. How relative and absolute risk of distant metastasis varies over time since diagnosis, as a function of treatment, age and tumour characteristics, has not been studied in detail. METHODS: A total of 9514 women under the age of 75 when diagnosed with breast cancer in Stockholm and Gotland regions during 1990-2006 were followed up for metastasis (mean follow-up=5.7 years). Time-dependent development of distant metastasis was analysed using flexible parametric survival models and presented as hazard ratio (HR) and cumulative risk. RESULTS: A total of 995 (10.4%) patients developed distant metastasis; the most common sites were skeleton (32.5%) and multiple sites (28.3%). Women younger than 50 years at diagnosis, with lymph node-positive, oestrogen receptor (ER)-negative, >20 mm tumours and treated only locally, had the highest risk of distant metastasis (0-5 years' cumulative risk =0.55; 95% confidence interval (CI): 0.47-0.64). Women older than 50 years at diagnosis, with ER-positive, lymph node-negative and ≤20-mm tumours, had the same and lowest cumulative risk of developing metastasis 0-5 and 5-10 years (cumulative risk=0.03; 95% CI: 0.02-0.04). In the period of 5-10 years after diagnosis, women with ER-positive, lymph node-positive and >20-mm tumours were at highest risk of distant recurrence. Women with ER-negative tumours showed a decline in risk during this period. CONCLUSION: Our data show no support for discontinuation at 5 years of clinical follow-up in breast cancer patients and suggest further investigation on differential clinical follow-up for different subgroups of patients.

Influence of hysterectomy on fistula formation in women with diverticulitis.

BACKGROUND: : Diverticulitis is a risk factor for fistula formation but little is known about the influence of hysterectomy in this association. A population-based nationwide matched cohort study was performed to determine the risk of fistula formation in hysterectomized women with, and without, diverticulitis. METHODS: : Women who had a hysterectomy between 1973 and 2003, and a matched control cohort, were identified from the Swedish Inpatient Register. Incidence of diverticulitis and fistula surgery was determined by cross-linkage to the Register, and risk was estimated using a Cox regression model. RESULTS: : In a cohort of 168 563 hysterectomized and 614 682 non-hysterectomized women (mean follow-up 11.0 and 11.5 years respectively), there were 14 051 cases of diverticulitis and 851 fistulas. Compared with women who had neither hysterectomy nor diverticulitis, the risk of fistula surgery increased fourfold in hysterectomized women without diverticulitis (hazard ratio (HR) 4.0 (95 per cent confidence interval (c.i.) 3.5 to 4.7)), sevenfold in non-hysterectomized women with diverticulitis (HR 7.6 (4.8 to 12.1)) and 25-fold in hysterectomized women with diverticulitis (HR 25.2 (15.5 to 41.2)). CONCLUSION: : Diverticulitis, and to a lesser extent hysterectomy, is strongly associated with the risk of fistula formation. Hysterectomized women with diverticulitis have the highest risk of developing surgically managed fistula.

Serum calcium and the risk of prostate cancer.

BACKGROUND: Recent studies have suggested an association between high dietary intake of calcium and the risk of prostate cancer. Calcium-rich diet has been suggested to affect the serum levels of Vitamin D, and thereby promote cancer. We conducted the largest study of the association between prediagnostic serum levels of calcium and the risk of prostate cancer. OUTLINE: We examined the incidence of prostate cancer in relation to prediagnostic serum calcium levels in a prospective cohort study of 22,391 healthy Swedish men, of which 1,539 incident cases of prostate cancer were diagnosed during the 30 years of follow-up until December 2006. MATERIAL AND METHODS: Serum levels of calcium were measured at baseline, and categorized into quartiles. Cox regression was used to estimate the adjusted hazard ratios (HR) with 95% confidence intervals (CI). RESULTS: We found no evidence of an association between prediagnostic serum levels of calcium and risk of prostate cancer (HR for trend = 0.99 [95% CI;0.94-1.03]). However, a moderate significant negative association was seen in men with a BMI above 25 and aged below 45 years at baseline (Highest vs. lowest quartile, HR = 0.63 [95% CI;0.40-0.99]). CONCLUSION: These data do not support the hypothesis that high serum calcium levels is a risk factor for prostate cancer. On the contrary, the data suggest that high serum levels of calcium in young overweight men may be a marker for a decreased risk of developing prostate cancer.

A long-term follow-up study on the natural course of oral leukoplakia in a Swedish population-based sample.

AIM: To assess the natural course of screening-detected oral leukoplakia (OL) among non-consulting individuals. METHODS: A cohort of 555 individuals with OL, confirmed in 1973-1974 during a population-based survey, were followed through January 2002 via record linkages with nationwide and essentially complete registers. A sample of 104 drawn from the 297 surviving cohort members who still were living in the area in 1993-1995 was invited to a re-examination. Sixty-seven of them attended. RESULTS: At the time of re-examination OL had disappeared in 29 (43%) individuals. There was a statistically significant association between cessation of/no smoking habits in 1993-1995 and the disappearance of OL. Never/previous daily smokers were thus over-represented among individuals whose OL had disappeared compared to those with persisting OL [n = 23 (82%) vs. n = 18 (47%), P < 0.01]. Eighteen (78%) of the twenty three non-smokers with disappearing OL had quit after the initial examination. One man and two women developed oral cancer during follow-up while 0.7 and 0.07, respectively, were expected. CONCLUSION: Smoking cessation was associated with an increased disappearance of OL. Hence, at least one-fourth had lesions that could be classified as tobacco-related. Small observed and expected numbers prohibited firm conclusions about a possible excess risk of developing oral cancer.

Airborne occupational exposures and risk of oesophageal and cardia adenocarcinoma.

BACKGROUND: The reasons for the increasing incidence of and strong male predominance in patients with oesophageal and cardia adenocarcinoma remain unclear. The authors hypothesised that airborne occupational exposures in male dominated industries might contribute. METHODS: In a nationwide Swedish population based case control study, 189 and 262 cases of oesophageal and cardia adenocarcinoma respectively, 167 cases of oesophageal squamous cell carcinoma, and 820 frequency matched controls underwent personal interviews. Based on each study participant's lifetime occupational history the authors assessed cumulative airborne occupational exposure for 10 agents, analysed individually and combined, by a deterministic additive model including probability, frequency, and intensity. Furthermore, occupations and industries of longest duration were analysed. Relative risks were estimated by odds ratios (OR), with 95% confidence intervals (CI), using conditional logistic regression, adjusted for potential confounders. RESULTS: Tendencies of positive associations were found between high exposure to pesticides and risk of oesophageal (OR 2.3 (95% CI 0.9 to 5.7)) and cardia adenocarcinoma (OR 2.1 (95% CI 1.0 to 4.6)). Among workers highly exposed to particular agents, a tendency of an increased risk of oesophageal squamous cell carcinoma was found. There was a twofold increased risk of oesophageal squamous cell carcinoma among concrete and construction workers (OR 2.2 (95% CI 1.1 to 4.2)) and a nearly fourfold increased risk of cardia adenocarcinoma among workers within the motor vehicle industry (OR 3.9 (95% CI 1.5 to 10.4)). An increased risk of oesophageal squamous cell carcinoma (OR 3.9 (95% CI 1.2 to 12.5)), and a tendency of an increased risk of cardia adenocarcinoma (OR 2.8 (95% CI 0.9 to 8.5)), were identified among hotel and restaurant workers. CONCLUSIONS: Specific airborne occupational exposures do not seem to be of major importance in the aetiology of oesophageal or cardia adenocarcinoma and are unlikely to contribute to the increasing incidence or the male predominance.

Helicobacter pylori status in family members as risk factors for infection in children.

This study aimed to disentangle the independent contributions of Helicobacter pylori infections in mothers, fathers and siblings to the risk for the infection in the 11-13 years age group. Index children from a cross-sectional Stockholm school survey and their family members completed questionnaires and contributed blood samples. H. pylori serostatus was determined with an enzyme-linked immunosorbent assay and immunoblot. Fifty-four seropositive and 108 seronegative index children were included and 480 out of 548 family members contributed blood. In multivariate logistic regression modelling, having an infected mother (OR 11.6, 95% CI 2.0-67.9) or at least one infected sibling (OR 8.1, 95% CI 1.8-37.3) were risk factors for index child infection, whilst the influence of infected fathers was non-significant. Birth in high-prevalence countries was an independent risk factor (OR 10.4, 95% CI 3.4-31.3). H. pylori infections in mothers and siblings and birth in high-prevalence countries stand out as strong markers of infection risk amongst children in Sweden.

Birth weight and risk of angina pectoris: analysis in Swedish twins.

OBJECTIVE: Intrauterine nutrition approximated by birth weight has been shown to be inversely associated with risk of coronary heart disease (CHD). By investigating the association within twin pairs discordant for disease, the influence of genetic and early environmental factors is substantially reduced. METHODS: We have investigated the association between birth weight and angina pectoris in same-sexed twins with known zygosity included in the population-based Swedish Twin Registry. Self-reports of birth weight and angina pectoris were collected in a telephone interview between 1998 and 2000. The cohort analyses were based on 4594 same-sexed twins, and the within-pair analyses included 55 dizygotic and 37 monozygotic twin pairs discordant for angina pectoris. Odds ratios (OR) and 95% confidence intervals (CI) were calculated by logistic regression. RESULTS: Compared with birth weight between 2.0 and 2.9 kg, low birth weight (<2.0 kg) was associated with increased risk of angina pectoris in the twin cohort, (OR: 1.46; 95% CI: 1.14-1.87), but after adjustment for potential confounders the risk decreased, and did not reach significance. Within twin pairs discordant for angina pectoris, low birth weight was significantly associated with increased risk of angina pectoris within dizygotic twins (adjusted OR: 5.73; 95% CI: 1.59-20.67), but not within monozygotic twins (adjusted OR: 1.20; 95% CI: 0.40-3.58). CONCLUSIONS: The results suggest that genetic differences associated with foetal growth and adult risk of CHD may have affected previously reported associations between birth weight and CHD.