Influence of comorbidity on chemotherapy use for early breast cancer: systematic review and meta-analysis

Purpose

The recent increase in the incidence of ductal carcinoma in situ (DCIS) has sparked debate over the classification and treatment of this disease. Although DCIS is considered a precursor lesion to invasive breast cancer, some DCIS may have more or less risk than is realized. In this study, we characterized the immune microenvironment in DCIS to determine if immune infiltrates are predictive of recurrence.

Methods

Fifty-two cases of high-grade DCIS (HG-DCIS), enriched for large lesions and a history of recurrence, were age matched with 65 cases of non-high-grade DCIS (nHG-DCIS). Immune infiltrates were characterized by single- or dual-color staining of FFPE sections for the following antigens: CD4, CD8, CD20, FoxP3, CD68, CD115, Mac387, MRC1, HLA-DR, and PCNA. Nuance multispectral imaging software was used for image acquisition. Protocols for automated image analysis were developed using CellProfiler. Immune cell populations associated with risk of recurrence were identified using classification and regression tree analysis.

Results

HG-DCIS had significantly higher percentages of FoxP3⁺ cells, CD68⁺ and CD68⁺PCNA⁺ macrophages, HLA-DR⁺ cells, CD4⁺ T cells, CD20⁺ B cells, and total tumor infiltrating lymphocytes compared to nHG-DCIS. A classification tree, generated from 16 immune cell populations and 8 clinical parameters, identified three immune cell populations associated with risk of recurrence: CD8⁺HLADR⁺ T cells, CD8⁺HLADR^? T cells, and CD115⁺ cells.

Conclusion

These findings suggest that the tumor immune microenvironment is an important factor in identifying DCIS cases with the highest risk for recurrence and that manipulating the immune microenvironment may be an efficacious strategy to alter or prevent disease progression.

     

Primary diffuse large B-cell lymphoma of the breast: prognostic factors and outcomes of a study by the International Extranodal Lymphoma Study Group.

BACKGROUND: Primary diffuse large B-cell lymphoma (DLBCL) of breast is rare. We aimed to define clinical features, prognostic factors, patterns of failure, and treatment outcomes. PATIENTS AND METHODS: A retrospective international study of 204 eligible patients presenting to the International Extranodal Lymphoma Study Group-affiliated institutions from 1980 to 2003. RESULTS: Median age was 64 years, with 95% of patients presenting with unilateral disease. Median overall survival (OS) was 8.0 years, and median progression-free survival 5.5 years. In multifactor analysis, favourable International Prognostic Index score, anthracycline-containing chemotherapy, and radiotherapy (RT) were significantly associated with longer OS (each P < or = 0.03). There was no benefit from mastectomy, as opposed to biopsy or lumpectomy only. At a median follow-up time of 5.5 years, 37% of patients had progressed--16% in the same or contralateral breast, 5% in the central nervous system, and 14% in other extranodal sites. CONCLUSIONS: The combination of limited surgery, anthracycline-containing chemotherapy, and involved-field RT produced the best outcome in the pre-rituximab era. A prospective trial on the basis of these results should be pursued to confirm these observations and to determine whether the impact of rituximab on the patterns of relapse and outcome parallels that of DLBCL presenting at other sites.     

High grade MALT-lymphoma of the breast.

A 65-year-old woman presented with a rapidly growing breast tumor, initially diagnosed as a carcinoma. Histology showed a breast lymphoma of high grade MALT-type. A lymphoma should always be considered in the differential diagnosis of a breast tumor, because it needs a different work-up and treatment. The subgroup of NHL of Mucosa-Associated-Lymphoid-Tissue origin has different clinical behaviour, as illustrated in this report.     

Metastatic relapse of stage I–III breast cancer in New Zealand

Purpose

This study aims to investigate the factors that influence the risk of metastatic relapse in women presenting with stage I-III breast cancer in New Zealand.

Methods

The study included women diagnosed with stage I–III breast cancer. Cumulative incidence of distant metastatic relapse was examined with the Kaplan–Meier method by cancer stage and subtype. Cox proportional hazards models were used to estimate the adjusted hazard ratio of developing recurrent metastatic breast cancer by cancer stage and biomarker subtype after adjustment for other factors.

Results

A total of 17,543 eligible women were identified. The 5-year cumulative incidence of metastatic recurrence was 3.7% for stage I, 13.3% for stage II and 30.9% for stage III disease. The adjusted hazard ratios (HR) of stage II and stage III breast cancer developing metastatic disease were 2.07 and 4.82 compared to stage I. The adjusted risk of distant metastatic relapse was highest for luminal B HER2- cancers (adjusted HR: 1.59 compared to luminal A disease). Higher grade cancers were associated with a higher risk of metastases. After adjustment, women aged 60–69 years and Asian women had the lowest risk of distant metastatic relapse.

Conclusions

The prognosis of women with locally invasive breast cancer differs greatly with the chance of developing metastatic disease depending on the stage of disease at diagnosis and the subtype. Grade of disease at diagnosis was also important. Māori or Pacific ethnicity did not influence the risk of developing metastatic disease, although Asian women seemed less likely to develop metastases.

     

Treatment and survival disparities by ethnicity in New Zealand women with stage I–III breast cancer tumour subtypes

Purpose

This study aims to look at the distribution of different subtypes of stage I–III breast cancer in Māori and Pacific versus non-Māori/Pacific women, and to examine cancer outcomes by ethnicity within these different subtypes.

Method

This study included 9,015 women diagnosed with stage I–III breast cancer between June 2000 and May 2013, recorded in the combined Waikato and Auckland Breast Cancer Registers, who had complete data on ER, PR and HER2 status. Five ER/PR/HER2 subtypes were defined. Kaplan–Meier method and Cox proportional hazards model were used to examine ethnic disparities in breast cancer-specific survival.

Results

Of the 9,015 women, 891 were Māori, 548 were Pacific and 7,576 others. Both Māori and Pacific women were less likely to have triple negative breast cancer compared to others (8.6, 8.9 vs. 13.0%). Pacific women were more than twice as likely to have ER?, PR? and HER2+ cancer than Māori and others (14.2 vs. 6.0%, 6.7%). After adjustment for age, year of diagnosis, stage, grade and treatment, the hazard ratios of breast cancer-specific mortality for Māori and Pacific women with ER+, PR+ and HER2? were 1.52 (95% CI 1.06–2.18) and 1.55 (95% CI 1.04–2.31) compared to others, respectively. Māori women with HER2+ cancer were twice more likely to die of their cancer than others.

Conclusions

Outcomes for Māori and Pacific women could be improved by better treatment regimens especially for those with HER2+ breast cancer and for women with ER+, PR+ and HER2? breast cancer.

     

What affects the public healthcare costs of breast cancer in New Zealand?

Backgrounds

The pressure to the healthcare system for providing ongoing monitoring and treatment for breast cancer survivors is increasing. This study aims to identify the factors that affect the public healthcare costs of stage I–III breast cancer and stage IV cancer in New Zealand.

Methods

We identified women diagnosed with invasive breast cancer between July 1, 2010 and June 30, 2018 and who received services in a public hospital. Patients were identified from the National Breast Cancer Register and/or New Zealand Cancer Registry and were linked to the national administrative datasets. A two-part model was used to identify the factors that affect the public healthcare costs of stage I–III breast cancer and stage IV cancer.

Results

We identified 16,977 stage I–III and 1,093 stage IV breast cancer patients eligible for this study. The costs of stage I–III cancer in the second to fifth year post diagnosis decreased over time, and the costs of stage IV cancer in the first year post diagnosis increased over time. After adjustment for other factors, the costs of stage I–IV cancer decreased with age but increased with cancer stage. HER2+ cancers had the highest costs, followed by triple negative cancers. After adjustment for other factors, Pacific and Asian women had lower costs, and Māori had similar costs compared to others. For stage I–III cancers, women living in nonmajor urban areas had a higher chance of incurring costs in follow-up years, and screen detected patients and patients having any services in a private hospital had a decreased probability of receiving any public healthcare services.

Conclusions

Pacific women had higher costs than others, but after adjustment for cancer stage, subtype, and other factors, they had lower costs than others. The early detection and better management of stage I–III breast cancer can lead to better outcome and lower costs in follow-up years.