Does diabetes affect breast cancer survival?

OBJECTIVES: The objective of this study is to investigate the influence of diabetes on breast cancer-specific survival among women with breast cancer in Aotearoa/New Zealand. METHODS: This study included women diagnosed with invasive breast cancer between 2005 and 2020, with their information documented in the Te Rehita Mate Utaetae-Breast Cancer Foundation National Register. Breast cancer survival curves for women with diabetes and those without diabetes were generated using the Kaplan-Meier method. The hazard ratio (HR) of breast cancer-specific mortality for women with diabetes compared to women without diabetes was estimated using the Cox proportional hazards model. RESULTS: For women with diabetes, the 5-year and 10-year of cancer-specific survival were 87% (95% CI: 85%-88%) and 79% (95% CI: 76%-81%) compared to 89% (95% CI: 89%-90%) and 84% (95% CI: 83%-85%) for women without diabetes. The HR of cancer-specific mortality for patients with diabetes compared to those without diabetes was 0.99 (95% CI: 0.89-1.11) after adjustment for patient demographics, tumor characteristics, and treatments. Age at cancer diagnosis and cancer stage had the biggest impact on the survival difference between the two groups. When stratified by cancer stage, the cancer-specific mortality between the two groups was similar. CONCLUSIONS: While differences in survival have been identified for women with diabetes when compared to women without diabetes, these are attributable to age and the finding that women with diabetes tend to present with more advanced disease at diagnosis. We did not find any difference in survival between the two groups due to differences in treatment.

The growing cancer burden: Age-period-cohort projections in Aotearoa New Zealand 2020-2044.

BACKGROUND: Cancer is a major cause of premature death and inequity, and global case numbers are rapidly expanding. This study projects future cancer numbers and incidence rates in Aotearoa New Zealand. METHODS: Age-period-cohort modelling was applied to 25-years of national data to project cancer cases and incidence trends from 2020 to 2044. Nationally mandated cancer registry data and official historical and projected population estimates were used, with sub-groups by age, sex, and ethnicity. RESULTS: Cancer diagnoses were projected to increase from 25,700 per year in 2015-2019 to 45,100 a year by 2040-44, a 76% increase (2.3% per annum). Across the same period, age-standardised cancer incidence increased by 9% (0.3% per annum) from 348 to 378 cancers per 100,000 person years, with greater increases for males (11%) than females (6%). Projected incidence trends varied substantially by cancer type, with several projected to change faster or in the opposite direction compared to projections from other countries. CONCLUSIONS: Increasing cancer numbers reinforces the critical need for both cancer prevention and treatment service planning activities. Investment in developing new ways of working and increasing the workforce are required for the health system to be able to afford and manage the future burden of cancer.

Cancer incidence, mortality and survival for Pacific Peoples in Aotearoa New Zealand.

AIMS: Pacific Peoples comprise over 16 culturally diverse ethnic groups and experience a disproportionate burden of preventable cancers, attributable to infectious diseases and obesity. This study aims to provide updated evidence on cancer incidence, mortality and survival rates among Pacific Peoples in Aotearoa New Zealand. METHODS: The study extracted incident cases of cancer diagnosed between 2007-2019 from the New Zealand Cancer Registry (NZCR) and linked them to the national Mortality Collection to determine individuals who died of cancer over the study period. The study also compared cancer survival rates between Pacific and European peoples in Aotearoa New Zealand. The most commonly diagnosed cancers and the most common causes of cancer death among Pacific Peoples were identified, and key findings were summarised. The European population was utilised as the comparator group for the analyses. The study employed a total ethnicity approach, wherein anyone with a record of Pacific ethnicity was classified as Total Pacific, regardless of other ethnicities. The age- and sex-standardised incidence and mortality rates were calculated, and 1-, 3- and 5-year survival rates determined. We used Cox proportional-hazards models to compare survival outcomes between Pacific and European peoples. CONCLUSIONS: The study results revealed that Pacific Peoples in Aotearoa New Zealand experience higher cancer incidence and a lower survival rate for several cancers, including lung, liver and stomach cancers, when compared to the European population. This study underscores the need for intervention to reduce the burden of cancer among Pacific Peoples and improve cancer outcomes. This study's findings can inform planning and delivery of interventions to achieve equitable outcomes across the cancer continuum for Pacific Peoples in Aotearoa New Zealand.

Who does not benefit from our national breast screening programme and who should have oversight?

The recent report on the delays for mammography encountered by women in the Wellington Region reminds us that the organisation of cancer screening is far from straightforward, and we highlight these complexities in our viewpoint article. Screening can reduce mortality from cancer, but it is costly, and the benefits are many years in the future. Cancer screening can result in some individuals being over-diagnosed and over-treated, can impact on the services for symptomatic patients and can exacerbate inequities. Reviewing the quality, safety and acceptability of our breast screening programme is important but there is a need to acknowledge the role of the resulting clinical services, including the opportunity cost to symptomatic patients who seek healthcare in the same system.

Impact of diabetes on surgery and radiotherapy for breast cancer.

PURPOSES: This study aims to examine whether diabetes has an impact on the use of surgery and adjuvant radiotherapy in treating women with localised breast cancer. METHODS: Women diagnosed with stage I-III breast cancer between 2005 and 2020 were identified from Te Rehita Mate Utaetae-Breast Cancer Foundation New Zealand National Register, with diabetes status determined using New Zealand's Virtual Diabetes Register. The cancer treatments examined included breast conserving surgery (BCS), mastectomy, breast reconstruction after mastectomy, and adjuvant radiotherapy after BCS. Logistic regression modelling was used to estimate the adjusted odds ratio (OR) and 95% confidence interval (95% CI) of having cancer treatment and treatment delay (> 31 days) for patients with diabetes at the time of cancer diagnosis compared to patients without diabetes. RESULTS: We identified 25,557 women diagnosed with stage I-III breast cancer in 2005-2020, including 2906 (11.4%) with diabetes. After adjustment for other factors, there was no significant difference overall in risk of women with diabetes having no surgery (OR 1.12, 95% CI 0.94-1.33), although for patients with stage I disease not having surgery was more likely (OR 1.45, 95% CI 1.05-2.00) in the diabetes group. Patients with diabetes were more likely to have their surgery delayed (adjusted OR of 1.16, 95% CI 1.05-1.27) and less likely to have reconstruction after mastectomy compared to the non-diabetes group-adjusted OR 0.54 (95% CI 0.35-0.84) for stage I cancer, 0.50 (95% CI 0.34-0.75) for stage II and 0.48 (95% CI 0.24-1.00) for stage III cancer. CONCLUSIONS: Diabetes is associated with a lower likelihood of receiving surgery and a greater delay to surgery. Women with diabetes are also less likely to have breast reconstruction after mastectomy. These differences need to be taken in to account when considering factors that may impact on the outcomes of women with diabetes especially for Maori, Pacific and Asian women.

Association of diabetes and breast cancer characteristics at diagnosis.

PURPOSE: This study aims to examine the association of diabetes and breast cancer characteristics at diagnosis in Aotearoa/New Zealand. METHODS: Patients diagnosed with invasive breast cancer between 2005 and 2020 were identified from the National Breast Cancer Register. Logistic regression modeling was used to estimate the adjusted odds ratio (OR) of having stage III-IV cancer and the OR of having stage IV cancer for women with diabetes compared to those without diabetes. The adjusted OR of having screen-detected breast cancers for patients aged 45-69 years with diabetes compared to patients without diabetes was estimated. RESULTS: 26,968 women were diagnosed with breast cancer, with 3,137 (11.6%) patients having diabetes at the time of cancer diagnosis. The probability of co-occurrence of diabetes and breast cancer increased with time. Maori, Pacific and Asian women were more likely to have diabetes than European/Others. The probability of having diabetes also increased with age. For patients with diabetes, the probability of being diagnosed with stage III-IV cancer and stage IV cancer was higher than for patients without diabetes (OR 1.14, 95% CI 1.03-1.27; and 1.17, 95% CI 1.00-1.38). Women aged 45-69 years with diabetes were more likely to have screen-detected cancer than those without diabetes (OR 1.13, 95% CI 1.02-1.26). CONCLUSIONS: The co-occurrence of diabetes and breast cancer is becoming more common. Overall there is a small but significant adverse impact of having advanced disease for women with diabetes that is found at the time of breast cancer diagnosis, and this may contribute to other inequities that occur in the treatment pathway that may impact on patient outcomes.

Adipose derived stem cell extracellular vesicles modulate primary human macrophages to an anti-inflammatory phenotype in vitro.

EVs released by adipose derived stem cells (ADSCs) have shown promise as a therapeutic for tissue repair because of their purported immune-regulatory properties. Extracellular vesicles (EVs) from ADSCs could be beneficial in improving graft retention rates for autologous fat grafting (AFG) post-mastectomy as, currently, grafted tissue rates are variable. Enriching grafted tissue with ADSC-EVs may improve retention rates by modulating macrophages resident within both the breast and lipoaspirate. We aimed to identify key macrophage phenotypes that are modulated by ADSC-EVs in vitro. ADSCs were isolated from lipoaspirates of women undergoing AFG and characterised by flow cytometry and differentiation potential. ADSC-EVs were isolated from culture media and characterised by tuneable resistive pulse sensing, transmission electron microscopy and Western blot. Primary monocyte-derived macrophages were polarized to an M1-like (GM-CSF, IFNγ), M2-like phenotype (M-CSF, IL-4) or maintained (M0-like; M-CSF) and ADSC-EVs were co-cultured with macrophages for 48 h. Flow cytometry and high-dimensional analysis clustered macrophages post co-culture. A manual gating strategy was generated to recapitulate these clusters and was applied to a repeat experimental run. Both runs were analysed to examine the prevalence of each cluster, representing a unique macrophage phenotype, with and without ADSC-EVs. Following the addition of ADSC-EVs, M0-like macrophages demonstrated a reciprocal shift of cell distribution from a cluster with a 'high inflammatory profile' (CD36+++CD206+++CD86+++; 16.5 ± 7.0%; p < 0.0001) to a cluster with a 'lower inflammatory profile' (CD36+CD206+CD86+; 35  ± 21.5%; p < 0.05). M1-like macrophages shifted from a cluster with a 'high inflammatory profile' (CD206++CD11b++CD36++CD163++; 26.1 ± 9.4%; p = 0.0024) to a 'lower inflammatory profile' (CD206+CD11b+CD36+CD163+; 72.8  ± 8.7%; p = 0.0007). There was no shift in M2-like clusters following ADSC-EV treatment. ADSC-EVs are complex regulators of macrophage phenotype that can shift macrophages away from a heightened pro-inflammatory state.

Cancer and diabetes co-occurrence: A national study with 44 million person-years of follow-up.

The number of new cases of cancer is increasing each year, and rates of diabetes mellitus are also increasing dramatically over time. It is not an unusual occurrence for an individual to have both cancer and diabetes at the same time, given they are both individually common, and that one condition can increase the risk of the other. In this manuscript, we use national-level diabetes (Virtual Diabetes Register) and cancer (New Zealand Cancer Registry) data on nearly five million individuals over 44 million person-years of follow-up to examine the occurrence of cancer amongst a national prevalent cohort of patients with diabetes. We completed this analysis separately by cancer for the 24 most commonly diagnosed cancers in Aotearoa New Zealand, and then compared the occurrence of cancer among those with diabetes to those without diabetes. We found that the rate of cancer was highest amongst those with diabetes for 21 of the 24 most common cancers diagnosed over our study period, with excess risk among those with diabetes ranging between 11% (non-Hodgkin's lymphoma) and 236% (liver cancer). The cancers with the greatest difference in incidence between those with diabetes and those without diabetes tended to be within the endocrine or gastrointestinal system, and/or had a strong relationship with obesity. However, in an absolute sense, due to the volume of breast, colorectal and lung cancers, prevention of the more modest excess cancer risk among those with diabetes (16%, 22% and 48%, respectively) would lead to a substantial overall reduction in the total burden of cancer in the population. Our findings reinforce the fact that diabetes prevention activities are also cancer prevention activities, and must therefore be prioritised and resourced in tandem.

Fat Grafting before Delayed Prophylactic Mastectomy and Immediate Implant Reconstruction for Patients at High Risk of Complications.

SUMMARY: The majority of patients undergoing bilateral prophylactic mastectomy request immediate implant-based breast reconstruction. Some patients, especially those with prior radiotherapy, are at increased risk of early cutaneous complications and implant loss. The authors developed the technique of primary fat grafting before delayed prophylactic mastectomy to minimize early complications for selective high-risk patients. They have completed 21 cases in 14 patients, 10 of whom had previous lumpectomy and radiation treatment for breast cancer. A single session of fat grafting, with a median injection volume of 250 ml (interquartile range, 200 to 300 ml), was performed a median period of 19 weeks (interquartile range, 16 to 28 weeks) before prophylactic mastectomy. All cases were direct-to-implant reconstruction using textured silicone implants. The median implant volume was 410 ml (interquartile range, 318 to 450 ml). A minor early complication developed in 14 percent of cases (three of 21), with no early implant loss. At a median follow-up of 9 months (interquartile range, 5 to 27 months), the authors found no cases of implant loss and an excellent or good aesthetic outcome (score of 5 or 4) in 16 of 21 cases (76 percent). Fat grafting before prophylactic mastectomy is a novel strategy to minimize early complications and avoid implant loss in patients at high risk of postoperative complications. . CLINICAL QUESTION/LEVEL OF EVIDENCE: Therapeutic, IV.

Salvaging the infected breast implant: results of a retrospective series of 80 consecutive cases.

BACKGROUND: Breast implants are widely used in reconstruction after breast cancer. Infection after implant reconstruction is a major complication, with rates ranging from 5 to 30%. This rate is less for pure cosmetic augmentation. Historically, infection of an implant mandated implant removal for sepsis control. An alternative is to attempt to salvage the infected implant. This path can be a long one, requiring surgery for washouts and prolonged antibiotic therapy. This article documents our experience of infected implant salvage over the last 13 years. METHODS: We conducted a retrospective analysis of all patients who developed a breast implant infection between January 2005 and January 2018. All patients had both clinical signs of infection and a positive bacteriological sample. Patients were divided into two groups: upfront medical therapy (including those requiring secondary surgical salvage) and primary surgery. The salvage procedure was defined as successful when the implant was still in place three months after the initial reconstruction. RESULTS: Eighty patients were included: 77 in the medical group and 3 in the surgical group. Overall, implant salvage was achieved in 88.8% of women (n=71). Of these, 73.8% (n=59) underwent medical treatment alone and 15% (n=12) underwent medical treatment followed by surgical management. The main causative organism was staphylococcus in 81.2%. When the infection was caused by a coagulase-negative staphylococcus, the rate of success was 98% (p<0.003). CONCLUSIONS: This case series reports that salvage of an infected breast implant was achievable in up to 90% of women presenting with a documented infection, the majority requiring antibiotic management only. Early intervention is central to success.

Cancer control in the Pacific: big challenges facing small island states.

This Series paper describes the current state of cancer control in Pacific island countries and territories (PICTs). PICTs are diverse but face common challenges of having small, geographically dispersed, isolated populations, with restricted resources, fragile ecological and economic systems, and overburdened health services. PICTs face a triple burden of infection-related cancers, rapid transition to lifestyle-related diseases, and ageing populations; additionally, PICTs are increasingly having to respond to natural disasters associated with climate change. In the Pacific region, cancer surveillance systems are generally weaker than those in high-income countries, and patients often present at advanced cancer stage. Many PICTs are unable to provide comprehensive cancer services, with some patients receiving cancer care in other countries where resources allow. Many PICTs do not have, or have poorly developed, cancer screening, pathology, oncology, surgical, and palliative care services, although some examples of innovative cancer planning, prevention, and treatment approaches have been developed in the region. To improve cancer outcomes, we recommend prioritising regional collaborative approaches, enhancing cervical cancer prevention, improving cancer surveillance and palliative care services, and developing targeted treatment capacity in the region.

The burden of non-melanoma skin cancers in Auckland, New Zealand.

BACKGROUND/OBJECTIVES: As the New Zealand Cancer Registry does not require mandatory reporting of non-melanoma skin cancers (NMSC), basal cell carcinomas (BCC) and squamous cell carcinomas (SCC), the clinical burden of these diseases is unknown. METHODS: A retrospective review of all patients with histopathology performed allowed us to estimate invasive BCC and SCC in the Auckland region in 2008 (population 1.44 million). RESULTS: During this period, a total of 21 236 NMSC were diagnosed among 13 996 patients, consisting of 5611 SCC lesions (26%) and 15 525 (74%) BCC. The Auckland incidence rates per 100 000 were 425 for SCC and 1177 for BCC. The overall rate of NMSC per 100 000 was 1906.5 (standardised to the census data of Australia 2001); 1385 for BCC and 522 for SCC. Using published data on incidence trends and population growth, we estimate that 29 000-33 000 NMSC would have been excised in Auckland in 2016, and 78 000-87 000 in New Zealand. CONCLUSION: Auckland has the highest reported incidence of invasive NMSC in the world. We believe that high-risk cutaneous SCC and complex BCC should be recorded. Our study provides information for clinicians and health economists on the scale of the problem.

Experience of imaging following laparoscopic sleeve gastrectomy.

BACKGROUND: We aimed to report our experience with upper gastrointestinal (UGI) contrast studies and computed tomography (CT) swallow studies after laparoscopic sleeve gastrectomy, and comment on the merits of each modality. METHOD: Retrospective review of all patients undergoing laparoscopic sleeve gastrectomy (LSG) in a New Zealand hospital between 2011 and 2014 was conducted. Over this time period, routine UGI was replaced by CT swallow studies. All medical records and radiology were reviewed and pertinent findings reported. RESULTS: Seventy-nine patients underwent LSG over this time period and one patient had to be excluded; 48 (61.5%) had a UGI study and 30 patients (38.5%) had CT swallow. There were no leaks in this study and no leaks became clinically significant. Sixteen of 30 patients (53.3%) undergoing CT swallow had significant incidental findings demonstrated on axial imaging that required follow-up. CONCLUSION: CT swallow can provide the same information as a UGI but has a significant rate of incidental findings. The rate of incidental pathology on CT is higher than that quoted in the general population. In a bariatric population, this may allow early detection and treatment of co-existent pathology.

Patterns of axillary lymph node metastases and recurrent disease in grade 1 breast cancer in a New Zealand cohort: Does ethnicity matter?

BACKGROUND: In New Zealand, Maori and Pacific women are more likely than New Zealand/European women to present at a younger age with larger tumours and metastatic disease. Survival rates are also differential by ethnicity. Many factors are believed to be responsible for this including differences in comorbidities, delays to presentation and delays in treatment. It is unclear whether these differences exist amongst women with grade 1 cancer in New Zealand. Therefore, we examined patterns of axillary nodal involvement, recurrent disease and mortality in grade 1 breast cancer in New Zealand women, and whether ethnicity was an important predictor for any of these outcomes. METHOD: Data was retrieved from the Auckland Breast Cancer Registry (ABCR) and the Waikato Breast Cancer Registry (WBCR) which are prospective, population-based databases. All women newly diagnosed with grade 1 primary invasive breast cancer between 1 June 2000 and 31 May 2013 were identified from the two registries. RESULTS: There were 2857 grade 1 breast cancers diagnosed over this time period. Axillary lymph nodes were involved in 19.0% of women, and 5.1% developed recurrent disease (locoregional or distant). Pacific and Maori women were more likely than NZ European women to have larger tumours and lymphovascular invasion (LVI). Predictors for axillary node involvement were tumour size greater than 10mm, LVI and non-screen detected cancers. Tumour size greater than 10mm, lobular carcinoma and BCS without radiotherapy were predictive of recurrent and or metastatic disease. Ethnicity was not observed to be an independent predictor for axillary nodal involvement, recurrent and/or metastatic disease, or breast cancer specific mortality amongst New Zealand women with grade 1 breast cancer. CONCLUSION: Ethnicity was not a predictor of axillary node involvement, recurrent disease or mortality in grade 1 breast cancer in our population.

Thyroid cancer in Pacific women in New Zealand.

AIM: To describe trends in incidence rates of thyroid cancer in New Zealand between 1981-2004 with a particular focus on Pacific women. METHOD: Linked census-cancer registration data was used to calculate age standardised cancer incidence rates for thyroid cancer. Both trends over time amongst Pacific women, and differences in rates between Pacific and European/Other women in New Zealand, were assessed. RESULTS: Rates of thyroid cancer in New Zealand were higher for women than men. The highest rates of thyroid cancer in were observed amongst Pacific women with a pooled age-standardised incidence rate of 18.5/100,000 (95%CI 14.6-22.4/100,000) compared to 5.2/100,000 (95% 4.8-5.5/100,000) for European/Other; SRR 3.58 (95%CI 2.87-4.47). Sparse data mean it is difficult to clearly identify a trend over time for Pacific women but European women experienced a 73% increase from 4.0/100,000 (95%CI 3.3-4.6/100,000) in 1981=1986 to 6.9/100,000 (95%CI 5.9-7.8/100,000) in 2001-2004 (Ptrend=0.05). CONCLUSIONS: Pacific women in New Zealand have the highest rates of thyroid cancer among resident ethnic groups. Risk was highest for Pacific women over 45 years of age. More research needs to be done looking at which specific ethnicities are driving rates of thyroid cancer in New Zealand and whether the risk is influenced by birthplace and age at migration to New Zealand.

Cancer in Pacific people in New Zealand.

PURPOSE: To describe cancer incidence rates among Pacific people living in New Zealand from 1981 to 2004. METHODS: Linked census-cancer registration data were used to calculate age-standardized cancer incidence rates for Pacific people. Both trends over time within Pacific people and differences in rates between Pacific and European/Other people in New Zealand were assessed. RESULTS: Pacific rates were higher for cancers of the cervix, endometrium, gallbladder, lip, mouth and pharynx, liver, lung, ovary, pancreas, stomach, and thyroid, and lower for colorectal, bladder, and testicular cancers and melanoma. Differences were large, ranging from a 90 % lower rate of melanoma to over seven times higher rate of liver cancer compared to European/Other. Breast and prostate cancers were the commonest malignancies for Pacific women and men, respectively. Important changes for Pacific women over time include a 64 % decrease in cervical cancer incidence (ptrend = 0.02) and a 245 % increase for lung cancer (ptrend = 0.02), while men had a 366 % increase in prostate cancer (ptrend = 0.02). CONCLUSIONS: Pacific people in New Zealand have a disproportionate cancer burden related to infectious diseases such as HPV and Hepatitis B. However, with escalating evidence for causal associations between diabetes, obesity, and physical inactivity with various cancers, the challenge will be to prevent these cancers from rising in Pacific people who have the highest rates of these conditions in New Zealand. Disparities for tobacco-related cancers support tobacco consumption as another important cause of cancer incidence disparity. Continued efforts are needed to reduce infectious disease and improve screening program uptake among Pacific people.

High rates of endometrial cancer among Pacific women in New Zealand: the role of diabetes, physical inactivity, and obesity.

PURPOSE: To determine the endometrial cancer rates, and the proportion attributable to diabetes mellitus (DM), physical inactivity, and overweight/obesity, by ethnicity with a focus on Pacific women in New Zealand. METHODS: Linked census-cancer records (1981-2004) were used to determine incidence rates of endometrial cancer by ethnicity. Health survey data (2006-2007) were used to determine risk factor prevalence by ethnicity. Relative risks for the association between diabetes, obesity, physical inactivity and endometrial cancer were sourced from published studies. Population attributable risk (PAR) methods, with Monte Carlo simulation, were used to estimate the PAR% by ethnicity and applied to 2001-2004 cancer rates. RESULTS: Pacific women had 2.61 (95 % confidence interval 2.22-3.05) times the endometrial cancer rate of European/Other women pooled over time, and the most rapidly increasing rates over time with the rate ratio increasing from 1.96 (1.14-3.37) in 1981/1986 to 3.78 (3.03-4.71) in 2001/2004 (p for trend = 0.14). Pacific women had the highest PAR% for DM, physical inactivity, and overweight/obesity (63.1 %), followed by Maori (58.6 %) and European/Other (48.6 %). Applying these PAR% to 2001-2004 endometrial cancer rates, the rate ratio comparing Pacific to European/Other endometrial cancer reduced from 3.8 for total cancer (attributable plus non-attributable) to 2.3 for non-attributable cancer, and the rate difference reduced by 79 % from 51 to 11 per 100,000. CONCLUSIONS: Pacific women have high endometrial cancer rates in New Zealand. Some, but not all, of the ethnic inequalities were explained by measured differences in obesity/overweight, DM, and physical inactivity.