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Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

ABSTRACT: Background: Studies have demonstrated worse breast cancer-specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account.

Materials and methods: Patients surgically treated for nonmetastasized breast cancer between 2003 and 2009 were selected from The Netherlands Cancer Registry. Cumulative incidences of recurrence were calculated considering death without distant recurrence as competing event. Fine and Gray analyses were performed to characterize the impact of age (70-74 [reference group], 75-79, and ?80?years) on recurrence risk.

Results: A total of 18,419 patients were included. Nine-year cumulative incidences of locoregional recurrence were 2.5%, 3.1%, and 2.9% in patients aged 70-74, 75-79, and ?80?years, and 9-year cumulative incidences of distant recurrence were 10.9%, 15.9%, and 12.7%, respectively. After adjustment for tumor and treatment characteristics, age was not associated with locoregional recurrence risk. For distant recurrence, patients aged 75-79?years remained at higher risk after adjustment for tumor and treatment characteristics (75-79?years subdistribution hazard ratio [sHR], 1.25; 95% confidence interval [CI], 1.11-1.41; ?80?years sHR, 1.03; 95% CI, 0.91-1.17).

Conclusion: Patients aged 75-79?years had a higher risk of distant recurrence than patients aged 70-74?years, despite the higher competing mortality. Individualizing treatment by using prediction tools that include competing mortality could improve outcome for older patients with breast cancer.

Implications for practice: In this population-based study of 18,419 surgically treated patients aged 70?years or older, patients aged 75-79?years were at higher risk of distant recurrence than were patients aged 70-74?years. This finding suggests that patients in this age category are undertreated. In contrast, it was also demonstrated that the risk of dying without a recurrence strongly increases with age, and patients with a high competing mortality risk are easily overtreated. To identify older patients who may benefit from more treatment, clinicians should therefore take competing mortality risk into account. Prediction tools could facilitate this and thereby improve treatment strategy.

SUBMITTER: de Boer AZ

PROVIDER: S-EPMC6964133 | biostudies-literature | 2020 Jan

REPOSITORIES: biostudies-literature

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Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

de Boer Anna Z AZ van der Hulst Heleen C HC de Glas Nienke A NA Marang-van de Mheen Perla J PJ Siesling Sabine S de Munck Linda L de Ligt Kelly M KM Portielje Johanneke E A JEA Portielje Johanneke E A JEA Bastiaannet Esther E Liefers Gerrit Jan GJ

The oncologist 20190912 1

<h4>Background</h4>Studies have demonstrated worse breast cancer-specific mortality with older age, despite an increasing risk of dying from other causes due to comorbidity (competing mortality). However, findings on the association between older age and recurrence risk are inconsistent. The aim of this study was to assess incidences of locoregional and distant recurrence by age, taking competing mortality into account.<h4>Materials and methods</h4>Patients surgically treated for nonmetastasized ...[more]

PMID: 31515242

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Project description:BackgroundPatients with isolated locoregional recurrences (ILRR) of breast cancer have a high risk of distant metastasis and death from breast cancer. We aimed to establish whether adjuvant chemotherapy improves the outcome of such patients.MethodsThe CALOR trial was a pragmatic, open-label, randomised trial that accrued patients with histologically proven and completely excised ILRR after unilateral breast cancer who had undergone a mastectomy or lumpectomy with clear surgical margins. Eligible patients were enrolled from hospitals worldwide and were centrally randomised (1:1) to chemotherapy (type selected by the investigator; multidrug for at least four courses recommended) or no chemotherapy, using permuted blocks, and stratified by previous chemotherapy, oestrogen-receptor and progesterone-receptor status, and location of ILRR. Patients with oestrogen-receptor-positive ILRR received adjuvant endocrine therapy, radiation therapy was mandated for patients with microscopically involved surgical margins, and anti-HER2 therapy was optional. The primary endpoint was disease-free survival. All analyses were by intention to treat. This study is registered with ClinicalTrials.gov, number NCT00074152.FindingsFrom Aug 22, 2003, to Jan 31, 2010, 85 patients were randomly assigned to receive chemotherapy and 77 were assigned to no chemotherapy. At a median follow-up of 4·9 years (IQR 3·6-6 ·0), 24 (28%) patients had disease-free survival events in the chemotherapy group compared with 34 (44%) in the no chemotherapy group. 5-year disease-free survival was 69% (95% CI 56-79) with chemotherapy versus 57% (44-67) without chemotherapy (hazard ratio 0·59 [95% CI 0·35-0·99]; p=0·046). Adjuvant chemotherapy was significantly more effective for women with oestrogen-receptor-negative ILRR (pinteraction=0·046), but analyses of disease-free survival according to the oestrogen-receptor status of the primary tumour were not statistically significant (pinteraction=0·43). Of the 81 patients who received chemotherapy, 12 (15%) had serious adverse events. The most common adverse events were neutropenia, febrile neutropenia, and intestinal infection.InterpretationAdjuvant chemotherapy should be recommended for patients with completely resected ILRR of breast cancer, especially if the recurrence is oestrogen-receptor negative.FundingUS Department of Health and Human Services, Swiss Group for Clinical Cancer Research (SAKK), Frontier Science and Technology Research Foundation, Australian and New Zealand Breast Cancer Trials Group, Swedish Cancer Society, Oncosuisse, Cancer Association of South Africa, Foundation for Clinical Research of Eastern Switzerland (OSKK), Grupo Español de Investigación en Cáncer de Mama (GEICAM), and the Dutch Breast Cancer Trialists' Group (BOOG).

Dataset Information

Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

Publications

Impact of Older Age and Comorbidity on Locoregional and Distant Breast Cancer Recurrence: A Large Population-Based Study.

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