Impact of the transition from screen-film to digital screening mammography on interval cancer characteristics and treatment – A population based study from the Netherlands

IntroductionIn most breast screening programmes screen-film mammography (SFM) has been replaced by full-field digital mammography (FFDM). We compared interval cancer characteristics at SFM and FFDM screening mammography.Patients and methodsWe included all 297 screen-detected and 104 interval cancers in 60,770 SFM examinations and 427 screen-detected and 124 interval cancers in 63,182 FFDM examinations, in women screened in the period 2008–2010. Breast imaging reports, biopsy results and surgical reports of all cancers were collected. Two radiologists reviewed prior and diagnostic mammograms of all interval cancers. They determined breast density, described mammographic abnormalities and classified interval cancers as missed, showing a minimal sign abnormality or true negative.ResultsThe referral rate and cancer detection at SFM were 1.5% and 4.9‰ respectively, compared to 3.0% (p < 0.001) and 6.6‰ (p < 0.001) at FFDM. Screening sensitivity was 74.1% at SFM (297/401, 95% confidence interval (CI) = 69.8–78.4%) and 77.5% at FFDM (427/551, 95% CI = 74.0–81.0%). Significantly more interval cancers were true negative at prior FFDM than at prior SFM screening mammography (65.3% (81/124) versus 47.1% (49/104), p = 0.02). For interval cancers following SFM or FFDM screening mammography, no significant differences were observed in breast density or mammographic abnormalities at the prior screen, tumour size, lymph node status, receptor status, Nottingham tumour grade or surgical treatment (mastectomy versus breast conserving therapy).ConclusionFFDM resulted in a significantly higher cancer detection rate, but sensitivity was similar for SFM and FFDM. Interval cancers are more likely to be true negative at prior FFDM than at prior SFM screening mammography, whereas their tumour characteristics and type of surgical treatment are comparable.     

Breast and prostate cancer survivors’ experiences of patient-centered cancer follow-up care from primary care physicians and oncologists

Purpose

Patient-physician relationships impact health care seeking and preventive screening behaviors among patients. At the end of active treatment some cancer survivors report feeling disconnected from their care team. This study explores cancer survivors’ experiences of patient-centered cancer follow-up care provided by primary care physicians (PCP) and oncologists (ONC).

Methods

Three hundred five early stage, breast and prostate cancer survivors at least 2 years post treatment were surveyed from four community hospital oncology programs in New Jersey. Participants reported receipt of patient-centered care measured by care coordination, comprehensiveness of care, and personal relationship with PCPs and ONCs.

Results

PCPs received higher ratings for coordination of care and comprehensive care than ONCs from all survivors (P?<?0.01). However, prostate and breast cancer survivors rated strengths of their personal bonds with the physicians differently. While prostate cancer survivors rated PCPs significantly higher for all items (P?<?0.028), breast cancer survivors rated ONCs significantly higher on four out of seven items including having been through a lot together, understanding what is important regarding health, knowing their medical history and taking their beliefs and wishes into account (P?<?0.036).

Conclusions

Prostate and breast cancer survivors report different experiences with their PCPs and oncologists around the comprehensiveness and coordination of their cancer follow-up care in addition to the strength of their relationships with their physicians.

Implications for Cancer Survivors

There are important differences in the experience of patient-centered care among cancer survivors that should be considered when planning care models and interventions for these different populations.

     

A reanalysis of cancer mortality in Canadian nuclear workers (1956–1994) based on revised exposure and cohort data

Background:

A 15-country study of nuclear workers reported significantly increased radiation-related risks of all cancers excluding leukaemia, with Canadian data a major factor behind the pooled results. We analysed mortality (1956–1994) in the updated Canadian cohort and provided revised risk estimates.

Methods:

Employment records were searched to verify and revise exposure data and to restore missing socioeconomic status. Excess relative risks per sievert (ERR/Sv) of recorded radiation dose and 95% confidence intervals (CIs) were estimated using Poisson regression.

Results:

A significant heterogeneity of the dose–response for solid cancer was identified (P=0.02), with 3088 early (1956–1964) Atomic Energy of Canada Limited (AECL) workers having a significant increase (ERR/Sv=7.87, 95% CI: 1.88, 19.5), and no evidence of radiation risk for 42 228 workers employed by three nuclear power plant companies and post-1964 AECL (ERR/Sv=−1.20, 95% CI: <−1.47, 2.39). Radiation risks of leukaemia were negative in early AECL workers and non-significantly increased in other workers. In analyses with separate terms for tritium and gamma doses, there was no evidence of increased risk from tritium exposure. All workers had mortality lower than the general population.

Conclusion:

Significantly increased risks for early AECL workers are most likely due to incomplete transfer of AECL dose records to the National Dose Registry. Analyses of the remainder of the Canadian nuclear workers (93.2%) provided no evidence of increased risk, but the risk estimate was compatible with estimates that form the basis of radiation protection standards. Study findings suggest that the revised Canadian cohort, with the exclusion of early AECL workers, would likely have an important effect on the 15-country pooled risk estimate of radiation-related risks of all cancer excluding leukaemia by substantially reducing the size of the point estimate and its significance.     

Breast cancer stem cells and epithelial mesenchymal plasticity – Implications for chemoresistance

Tumour heterogeneity is a key characteristic of cancer and has significant implications relating to tumour response to chemotherapy as well as patient prognosis and potential relapse. It is being increasingly accepted that tumours are clonal in origin, suggestive of a tumour arising from a deregulated or mutated cell. Cancer stem cells (CSC) possess these capabilities, and with appropriate intracellular triggers and/or signalling from extracellular environments, can purportedly differentiate to initiate tumour formation. Additionally through epithelial mesenchymal plasticity (EMP), where cells gain and maintain characteristics of both epithelial and mesenchymal cell types, epithelial-derived tumour cells have been shown to de-differentiate to acquire cancer stem attributes, which also impart chemotherapy resistance. This new paradigm places EMP centrally in the process of tumour progression and metastasis, as well as modulating drug response to current forms of chemotherapy. Furthermore, EMP and CSCs have been identified in cancers arising from different tissue types making it a possible generic therapeutic target in cancer biology. Using breast cancer (BrCa) as an example, we summarise here the current understanding of CSCs, the role of EMP in cancer biology – especially in CSCs and different molecular subtypes, and the implications this has for current and future cancer treatment strategies.     

Breast cancer risk assessment in the Czech female population – an adjustment of the original Gail model

Summary Background. Several mathematical models have been developed for predicting individual breast cancer risk. Such models can help clinicians to choose appropriate preventive and therapeutic interventions for each patient. Unfortunately, the validity of these models has not been tested outside the USA.   Methods. The authors describe a case–control study in the Czech Republic with a similar design to that of the US Breast Cancer Detection and Demonstration Project (BCDDP). The main objective of the study was to evaluate the validity of the Gail model in the Czech female population, and to develop a local model using the same statistical approach as the Gail model. Between November 2000 and May 2004, 14,566 questionnaires containing case history data from both healthy women (control group) and women with breast cancer were collected. Case–control age-matched pairs (n = 4598) have subsequently been matched and analyzed.   Results. Our results show that the original Gail model was not able to properly distinguish between controls and breast cancer cases in the Czech female population. Based on paired data, the mean 5-year and life-time breast cancer risk was 1.379 ± 0.668 and 7.990 ± 3.184 in the control group and 1.375 ± 0.692 and 8.028 ± 3.506 in the patients with breast cancer group. The original Gail model was also not able to properly describe age-specific baseline risk of breast cancer development in the Czech population. In response the authors developed two variants of modified/locally adjusted models.   Conclusion. The original Gail model is not an accurate breast cancer risk assessment tool for the Czech female population.     

Weekday of gastrectomy for cancer in relation to mortality and oncological outcomes – A Dutch population-based cohort study

Background

Some studies demonstrate that high-complex surgeries performed later in the week are associated with higher postoperative mortality and worse long-term survival. The aim of this cohort study was to determine whether weekday influences outcomes in patients undergoing gastrectomy for cancer.

Regulation of exosome release from mammary epithelial and breast cancer cells – A new regulatory pathway

PurposeExosomes are small 50–100 nm sized extracellular vesicles released from normal and tumour cells and are a source of a new intercellular communication pathway. Tumour exosomes promote tumour growth and progression. What regulates the release and homoeostatic levels of exosomes, in cancer, in body fluids remains undefined.MethodsWe utilised a human mammary epithelial cell line (HMEC B42) and a breast cancer cell line derived from it (B42 clone 16) to investigate exosome production and regulation. Exosome numbers were quantified using a Nanosight LM10 and measured in culture supernatants in the absence and presence of exosomes in the medium. Concentrated suspensions of exosomes from the normal mammary epithelial cells, the breast cancer cells and bladder cancer cells were used. The interaction of exosomes with tumour cells was also investigated using fluorescently labelled exosomes.ResultsExosome release from normal human mammary epithelial cells and breast cancer cells is regulated by the presence of exosomes, derived from their own cells, in the extracellular environment of the cells. Exosomes from normal mammary epithelial cells also inhibit exosome secretion by breast cancer cells, which occurs in a tissue specific manner. Labelled exosomes from mammary epithelial cells are internalised into the tumour cells implicating a dynamic equilibrium and suggesting a mechanism for feedback control.ConclusionsThese data suggest a previously unknown novel feedback regulatory mechanism for controlling exosome release, which may highlight a new therapeutic approach to controlling the deleterious effects of tumour exosomes. This regulatory mechanism is likely to be generic to other tumours.     

Socio-economic factors and breast cancer survival – a population-based cohort study (Sweden)

Objective: To assess the influence of socio-economic factors on breast cancer survival in Sweden, a country with population-based mammography screening and a uniform health care system aiming to provide care to all on equal terms.Methods: All women with a first diagnosis of invasive breast cancer in Sweden in 1993 were identified in the Swedish Cancer Register. Their sociodemographic characteristics were determined by record linkages to the 1970, 1980, 1985 and 1990 Census databases, and a nationwide Fertility Register. Information on tumor characteristics at diagnosis was obtained from five Swedish Regional Cancer Registers. Survival status on 31 December 1998, was assessed through follow-up in the Swedish Cause of Death Register.Results: Of totally 4645 eligible women diagnosed with breast cancer in 1993, 772 had died from breast cancer through 1998. After adjustment for tumor characteristics and age, risk of death was 37 higher among women of low compared to high socio-economic status (HR high vs. low 0.73; 95 CI: 0.54–0.99). This difference was most pronounced in women less than 50 years at diagnosis.Conclusions: These results show that socio-economic disparities in breast cancer survival prevail even in this relatively homogenous society, offering outreach mammography and standardised treatment regimens in a tax-funded health care system.Financial support: This study was supported by the Swedish Council for Social Research (grant No. 97-0221), Karolinska Institutet Research Funds and the Swedish Cancer Society.     

Sarcopenia in pancreatic cancer – effects on surgical outcomes and chemotherapy

Sarcopenia is found in up to 65% of pancreatic cancer patients. The definition and diagnostic methods for sarcopenia have changed over the years, and the measurement of skeletal muscle mass with cross-sectional imaging has become the most popular way of assessment, although the parameters measured vary among different studies. It is still debatable that there is an association between sarcopenia and postoperative pancreatic fistula, but most studies showed a higher risk in patients with sarcopenic obesity. Long-term survival is worse in sarcopenic patients, as shown by meta-analysis. Sarcopenia is also associated with decreased survival and higher toxicity in patients receiving chemotherapy, and chemotherapy also tends to potentiate sarcopenia. Treatment for sarcopenia still remains an area for research, although oral supplements, nutritional modifications and exercise training have been shown to improve sarcopenia.     

Treatment and pattern of bone metastases in 1094 patients with advanced breast cancer – Results from the prospective German Tumour Registry Breast Cancer cohort study

A high proportion of patients with breast cancer develop bone metastases, yet data on routine treatment with bone-targeted agents (BTA) are rare. We report real-life outcome data of patients with breast cancer metastasised to the bone treated by office-based oncologists in Germany.The ongoing, prospective, multicentre, population-based cohort study Tumour Registry Breast Cancer (TMK) was started in 2007 in 140 centres across Germany.This interim analysis of 1094 patients with bone metastases revealed differences among the tumour subtypes: at start of first-line therapy, 36% of the patients with hormone receptor (HR)-positive and only 20% of the patients with HR-negative tumours presented with bone-only metastasis. The majority of patients with bone metastases (89%, n = 976) received BTA therapy. In 2014–2015, 37% of the patients received the bisphosphonate zoledronic acid and 36% the antibody denosumab. Median duration of BTA therapy was 20 months (interquartile range 31.5 months), starting a median of 3 weeks after diagnosis of bone metastases, and ending a median of 7 weeks before death. The median overall survival (OS) also varied among the types of metastasis at start of first-line therapy ranging from 54 months (95% confidence interval [CI] 37.6–70.8), 38 months (95% CI 29.4–44.2) to 28 months (95% CI 24.2–31.0) for patients with bone-only metastases, non-visceral with or without bone metastases and visceral with or without bone metastases respectively.We show that choice and duration of BTA therapies are in conformity with guidelines applicable in Germany. To our knowledge, this is the first presentation of data on incidence, metastatic pattern, treatment and survival of patients with bone metastases in routine practice.     

Clear Cell Carcinoma of the Breast: A Rare Breast Cancer Subtype – Case Report and Literature Review

BackgroundGlycogen-rich clear cell breast carcinoma is a rare histological breast cancer subtype. Its prognosis may vary depending on specific clinical and pathological characteristics such as low grade, strong positivity of estrogen receptor (ER) expression and early diagnosis.ConclusionsGlycogen-rich clear cell carcinoma of the breast is a rare tumor. Early diagnosis, absence of lymph node metastases and ER/PR positivity are associated with a better prognosis, as in other common breast cancer subtypes.Key Words: Breast cancer, Glycogen-rich clear cell carcinoma     

Ukrain – a new cancer cure? A systematic review of randomised clinical trials

Background  

Ukrain is an anticancer drug based on the extract of the plant Chelidonium majus L. Numerous pre-clinical and clinical investigations seem to suggest that Ukrain is pharmacologically active and clinically effective. We wanted therefore to critically evaluate the clinical trial data in the form of a systematic review.     

The impact of colorectal surgery on health-related quality of life in older functionally dependent patients with cancer – A longitudinal follow-up study

BackgroundOlder patients who are functionally compromised or frail may be at risk for loss of quality of life (QoL) after colorectal cancer (CRC) surgery. We prospectively studied health-related QoL (HRQoL) and its association with functional dependency on multiple time points before and after CRC surgery.MethodsIncluded were patients aged 70 years and older who underwent elective CRC surgery between 2014 and 2015 in combination with an oncogeriatric care path. HRQoL (EORTC QLQ-C30 and CR38) and activities of daily living (ADL, Barthel Index) were measured at four time-points; prior to (T0) and at 3 (T3), 6 (T6), and 12 (T12) months after surgery. Functional dependency was defined as a Barthel Index <19. Using mixed-model regression analysis associations between dependency, time and HRQoL outcomes were tested and corrected for confounders.ResultsResponse rate was 67% (n = 106) to two or more questionnaires; 26 (25%) patients were functionally dependent. Overall, functionally independent patients experienced a higher HRQoL than dependent patients. Compared to T0, significant and clinically relevant improvements in HRQoL after surgery were observed in functionally dependent patients: better role functioning, a higher global health, a higher summary score, less fatigue and less gastrointestinal problems (p < .05). In functional independent patients, we observed no clinically relevant change in HRQoL.ConclusionColorectal surgery embedded in geriatric-oncological care has a positive impact on HRQoL in older functionally dependent patients with cancer. Moderate functional dependency should not be considered a generic reason for withholding surgical treatment. Information derived from this study could be used in shared decision making.     

Internal mammary lymph drainage and sentinel node biopsy in breast cancer – A study on 1008 patients

Introduction

Nowadays, axillary sentinel node (SN) biopsy is a standard procedure in the staging of breast cancer. Although the internal mammary (IM) lymph node status is a major independent prognostic factor in breast cancer patients, sampling of IM sentinel nodes (IMSNs) is not performed routinely. The aim of this study was to determine the likelihood of finding IM lymph node metastases in case of IM hotspots on lymphoscintigraphy and evaluate the relevance of IMSN biopsy as a method to improve staging.

Patients and methods

Between April 1997 and May 2006, a total of 1008 consecutive patients with clinically node-negative operable primary breast cancer were enrolled in a prospective study on SN biopsy. Both axillary and IMSNs were sampled, based on lymphoscintigraphy, intraoperative gamma probe detection and blue dye mapping, using 10 mCi (370 MBq) ^99mTc-nanocolloid injected peritumorally, and 0.5–1.0 ml Patent Blue V injected intradermally.

Results

Lymphoscintigraphy showed axillary sentinel nodes in 98% (989/1008) and IMSNs in 20% of the patients (196/1008). Sampling the IM basin, as based on the results of lymphoscintigraphy, was successful in 71% of the patients (139/196) and revealed metastases in 22% (31/139). In 29% of the patients with positive IMSNs (9/31) no axillary metastases were found.

Conclusion

Evaluation of IMSNs improves nodal staging in breast cancer. Patients with IM hotspots on lymphoscintigraphy have a substantial risk (22%) of metastatic involvement of the IM chain. In addition, true IM node-negative patients can be spared the morbidity associated with adjuvant radiotherapy.     

Has the association between hysterectomy and ovarian cancer changed over time? A systematic review and meta-analysis

Until recently most studies suggested that hysterectomy with ovarian conservation was associated with a decreased risk of ovarian cancer. However, several recent studies have reported modestly increased risks of ovarian cancer following hysterectomy. Given that as many as 35% of women will have a hysterectomy, the nature of the association requires clarification. We conducted a systematic review and meta-analysis of the published literature on the relationship between hysterectomy and ovarian cancer to investigate whether there has been a temporal change in the association. Twenty observational studies that have reported a quantitative assessment of the association between hysterectomy and risk of histologically-confirmed ovarian cancer were included in the meta-analysis. The overall relative risk (RR) estimate was 0.81 (95% confidence interval (CI) 0.72–0.92) suggesting hysterectomy decreases the risk of ovarian cancer. However, there was significant heterogeneity in the results (I² = 74%). Our exploration of sources of heterogeneity and metaregression showed that median year of cancer diagnosis of included cases explained most of the heterogeneity relative risk (RR = 0.70 (95% CI 0.65–0.76) for median year diagnosis pre 2000; RR = 1.18 (95% CI 1.06–1.31) for post 2000). This study shows that there has been a temporal shift in the association between hysterectomy and risk of ovarian cancer. One explanation may be the trend away from hysterectomy in younger women. Other speculative possibilities include the decline in oophorectomy rates and the use of oestrogen-only hormone replacement therapy in hysterectomised women. Until further evidence becomes available, clinicians should not advise women that a hysterectomy without salpingo-oophorectomy will favourably influence their future risk of ovarian cancer.     

Comment on “Crosstalk between gut microbiota and COVID-19 impacts pancreatic cancer progression”

The coronavirus disease 2019 (COVID-19) pandemic has become a global burden, further exacerbating the occurrence of risk events in cancer patients. The high risk of death from pancreatic cancer makes it one of the most lethal malignancies. Recently, it was reported in the World Journal of Gastrointestinal Oncology that COVID-19 influences pancreatic cancer progression via the lung–gut–pancreatic axis, and the authors provided insights into the intrinsic crosstalk mechanisms in which the gut microbiota is involved, the characteristics and effects of inflammatory factors, and immunotherapeutic strategies for treating both diseases. Here, we review the latest cutting-edge researches in the field of the lung-gut-pancreatic axis and discuss future perspectives to address the severe survival challenges posed by the COVID-19 pandemic in patients with pancreatic cancer.     

Can we trust cancer information on the Internet? – A comparison of interactive cancer risk sites

Objective:To investigate the prevalence and quality of interactive cancer risk sites on the Internet.Methods:A cancer risk site was defined as a website that gave an estimate of the individual risk of developing cancer. Six search engines and one Meta crawler were used to search the Internet for cancer risk sites (including breast, prostate, colon, and lung cancer). A set of defined quality criteria for health related websites was used to evaluate the websites during 2001 and 2002.Results:The number of cancer risk sites, as defined above, increased by 50% between 2001 and 2002. Only two out of 22 cancer risk sites fulfilled the quality criteria adequately. No signs of a change in trend (with regard to the quality criteria met) were noted in January 2005Conclusions:The overall quality of the documentation on the cancer risk sites was poor and no improvement was seen during the study period. The majority of the cancer risk sites do not give reliable risk estimates.