Recurrence dynamics of breast cancer according to baseline body mass index

Biganzoli, Elia; Desmedt, Christine; Fornili, Marco; Azambuja, Evandro de; Cornez, Nathalie; Ries, F.; Closon-Dejardin, Marie Thérèse; Kerger, Joseph; Focan, C.; Leo, Angelo Di; Nogaret, Jean Marie; Sotiriou, Christos; Piccart, Martine; Demicheli, Romano

doi:10.1016/j.ejca.2017.10.007

Cited by 39 publications

(30 citation statements)

References 44 publications

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“…Moreover, premenopausal and postmenopausal, overweight and obese patients with breast cancer are generally at higher risk of recurrence and resistance to therapy [1, 2, 12, 50–52]. Biganzoli and collaborators used data from the prospective “three-arms” trial with very long follow up to show that the patient’s BMI at diagnosis is associated with specific recurrence patterns over time [53]. They observed for example that obese patients present with at least two peaks of recurrences, one early and one late.…”

Section: Discussionmentioning

confidence: 99%

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

et al. 2018

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BackgroundObesity is a strong predictor of poor prognosis in breast cancer, especially in postmenopausal women. In particular, tumors in obese patients tend to seed more distant metastases, although the biology behind this observation remains poorly understood.MethodsTo elucidate the effects of the obese microenvironment on metastatic spread, we ovariectomized C57BL/6 J female mice and fed them either a regular diet (RD) or a high-fat diet (HFD) to generate a postmenopausal diet-induced obesity model. We then studied tumor progression to metastasis of Py230 and EO771 grafts. We analyzed and phenotyped the RD and HFD tumors and the surrounding adipose tissue by flow cytometry, qPCR, immunohistochemistry (IHC) and western blot. The influence of the microenvironment on tumor cells was assessed by performing cross-transplantation of RD and HFD tumor cells into other RD and HFD mice. The results were analyzed using the unpaired Student t test when comparing two variables, otherwise we used one-way or two-way analysis of variance. The relationship between two variables was calculated using correlation coefficients.ResultsOur results show that tumors in obese mice grow faster, are also less vascularized, more hypoxic, of higher grade and enriched in CD11b+Ly6G+ neutrophils. Collectively, this favors induction of the epithelial-to-mesenchymal transition and progression to claudin-low breast cancer, a subtype of triple-negative breast cancer that is enriched in cancer stem cells. Interestingly, transplanting HFD-derived tumor cells in RD mice transfers enhanced tumor growth and lung metastasis formation.ConclusionsThese data indicate that a pro-metastatic effect of obesity is acquired by the tumor cells in the primary tumor independently of the microenvironment of the secondary site.Graphical abstractEffects of postmenopausal obesity on primary breast cancer tumoursᅟElectronic supplementary materialThe online version of this article (10.1186/s13058-018-1029-4) contains supplementary material, which is available to authorized users.

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Section: Discussionmentioning

confidence: 99%

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

et al. 2018

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“…In a study by Eliassen et al [18], while there was a 12% increased risk for breast cancer among overweight, postmenopausal women, this increased risk rose to 25% in obese, postmenopausal women. Evidence links obesity not only to the elevated risk of breast cancer, but also to breast cancer recurrence [19] and mortality [20]. While some studies suggest that obesity in pre-menopausal women has no effect or actually reduces the risk of breast cancer [16, 21, 22], obesity is associated with worse outcomes for both pre- and postmenopausal breast cancer patients, including a 30% higher risk of death relative to breast cancer patients with a normal BMI [16, 20].…”

Section: Obesity and Breast Cancermentioning

confidence: 99%

Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk

Seiler

Chen

Brown

et al. 2018

Curr Breast Cancer Rep

100

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Purpose of Review To synthesize the critical role of obesity-associated inflammation, dietary factors, and nutrition in determining breast cancer risk. Recent Findings Obesity-associated inflammation is strongly linked to breast cancer risk and progression, largely via two processes: inflammatory pathways and dysregulated metabolism. Cytokine production in excess adipose tissues creates a chronic inflammatory microenvironment, which favors tumor development. Lifestyle factors, including diet, have long been recognized as important determinants of breast cancer risk and mortality. Summary Obesity increases the risk of developing breast cancer in both pre- and postmenopausal women and also negatively affects breast cancer recurrence and survival. Poor dietary habits characterized by the high intake of refined starches, sugar, and both saturated and trans-saturated fats, as well as the low intake of omega-3 fatty acids, natural antioxidants, and fiber, modulate inflammation and, thereby, appear to be linked to increased risk of breast cancer and mortality.

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“…A recent experimental study also suggested a new mechanism in which exercise reduces inflammatory cell production via the reduction of leptin levels and instruction of the hematopoietic progenitor cells [14]. Therefore, on the basis of the review propositions [12] and following our previous research [15,16], we hypothesize that while short term pharmacological interventions as adjuvant chemotherapy may act mainly on early recurrences [5] (possibly associated to surgery-related acute inflammatory processes), physical exercise might deal with later recurrences through its modulatory effects on immune processes, possibly related to chronic inflammation.…”

Section: Discussionmentioning

confidence: 77%

Impact of physical activity on recurrence dynamics in early breast cancer patients

Biganzoli

Desmedt

Demicheli

2020

Preprint

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Background Several studies have suggested that pre and/or postdiagnosis physical activity can reduce the risk of recurrence in breast cancer patients, however its effect according to follow-up time has not yet been investigated. Methods We analyzed recurrence and mortality dynamics in randomized clinical trials (RCTs) from Australia and Canada. The combined Australian RCTs evaluated, at median follow-up of 8.3 years, an 8-month pragmatic exercise intervention in 337 women with newly diagnosed breast cancer, while the Canadian RCT evaluated, at median follow-up of 7.4 years, supervised aerobic or resistance exercise during chemotherapy in 242 patients. For each RCT, the control arm consisted of patients undergoing usual care. We estimated the event dynamics by the discrete hazard function, through flexible regression of yearly conditional event probabilities with generalized additive models. Results In the considered RCTs, the recurrence and mortality risk of patients enrolled in the physical activity arm was stably reduced at medium/long term after five year of follow-up. In the Australian RCTs where patients were recruited by urban versus rural area, the latter group did not display benefit from physical activity. Estimated Odds Ratios (95% Confidence Intervals) for Disease Free Survival (DFS) in urban women were 0.63 (0.22-1.85); 0.27 (0.079-0.90); 0.11 (0.013-0.96) at the 3rd, 5th and 7th year of follow-up, respectively. For rural women, DFS patterns were overlapping with ORs approximating 1 at the different years of follow-up. Although not reaching statistical evidence, the estimates in the Canadian trial were in line with the results from the Australian urban women with ORs (95% CI) forDFS of 0.70 (0.33-1.50); 0.47 (0.19-1.18); 0.32 (0.077-1.29) at 3rd, 5th, 7th follow-up year, respectively. Conclusions While we acknowledge that the analyzed RCTs were not designed for investigating disease recurrence over time, these results support the evidence that physical activity reduces the risk of developing medium/long-term metastases. Additional translational research is needed to clarify the mechanisms underlying these observations.

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Recurrence dynamics of breast cancer according to baseline body mass index

Cited by 39 publications

References 44 publications

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

Obesity promotes the expansion of metastasis-initiating cells in breast cancer

Obesity, Dietary Factors, Nutrition, and Breast Cancer Risk

Impact of physical activity on recurrence dynamics in early breast cancer patients

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