scholarly journals Metabolic consequences of perioperative oral carbohydrates in breast cancer patients — an explorative study

BMC Cancer ◽  
2019 ◽  
Vol 19 (1) ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Tone Frost Bathen ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Breast Cancer Patients ◽  
Positive Correlation ◽  
Explorative Study ◽  
Er Positive ◽  
Lactate And Pyruvate ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present explorative study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Methods The study setting was on university hospital level with primary and secondary care functions in south-west Norway. Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n = 25) or standard pre-operative fasting (n = 35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n = 18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p = 0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r = 0.680; p = 0.002). In all tumors (n = 29), glutamate was increased in tumors with high proliferation (t-test; p = 0.009), independent of intervention group. Moreover, there was a positive correlation between tumor size and proliferation markers in the carbohydrate group only. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Trial of registration ClinicalTrials.gov; NCT03886389. Retrospectively registered March 22, 2019.

scholarly journals Metabolic consequences of perioperative oral carbohydrates in breast cancer patients: An explorative study

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Tone Frost Bathen ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Magic Angle ◽  
Breast Cancer Patients ◽  
Explorative Study ◽  
Er Positive ◽  
Lactate And Pyruvate ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background: The metabolic consequences of preoperative carbohydrate load in breast cancer patients are not known. The present study investigated the systemic and tumor metabolic changes after preoperative per-oral carbohydrate load and their influence on tumor characteristics and survival. Design: Explorative study. Setting: University hospital with primary and secondary care functions in south-west Norway.Interventions and Outcome Measures: Serum and tumor tissue were sampled from a population-based cohort of 60 patients with operable breast cancer who were randomized to either per-oral carbohydrate load (preOp™; n=25) or standard pre-operative fasting (n=35) before surgery. Magnetic resonance (MR) metabolomics was performed on serum samples from all patients and high-resolution magic angle spinning (HR-MAS) MR analysis on 13 tumor samples available from the fasting group and 16 tumor samples from the carbohydrate group. Results: Fourteen of 28 metabolites were differently expressed between fasting and carbohydrate groups. Partial least squares discriminant analysis showed a significant difference in the metabolic profile between the fasting and carbohydrate groups, compatible with the endocrine effects of insulin (i.e., increased serum-lactate and pyruvate and decreased ketone bodies and amino acids in the carbohydrate group). Among ER-positive tumors (n=18), glutathione was significantly elevated in the carbohydrate group compared to the fasting group (p=0.002), with a positive correlation between preoperative S-insulin levels and the glutathione content in tumors (r=0.680; p=0.002). In all tumors (n=29), glutamate was increased in tumors with high proliferation (t-test; p=0.009), independent of intervention group. Patients with ER-positive / T2 tumors and high tumor glutathione (≥1.09), high S-lactate (≥56.9), and high S-pyruvate (≥12.5) had inferior clinical outcomes regarding relapse-free survival, breast cancer-specific survival, and overall survival. Moreover, Integrated Pathway Analysis (IPA) in serum revealed activation of five major anabolic metabolic networks contributing to proliferation and growth. Conclusions: Preoperative carbohydrate load increases systemic levels of lactate and pyruvate and tumor levels of glutathione and glutamate in ER-positive patients. These biological changes may contribute to the inferior clinical outcomes observed in luminal T2 breast cancer patients. Registration of trial: CliniTrials.gov; NCT03886389. Retrospectively registered March 22, 2019. Available at: https://clinicaltrials.gov/ct2/show/NCT03886389?cond=Breast+cancer+diet&rank=1

scholarly journals Impact of BMI for clinical outcomes in Japanese breast cancer patients

2020 ◽  
Vol 50 (3) ◽  
pp. 230-240
Author(s):  
Naomi Gondo ◽  
Masataka Sawaki ◽  
Masaya Hattori ◽  
Akiyo Yoshimura ◽  
Haruru Kotani ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Clinical Outcomes ◽  
Disease Free Survival ◽  
Overweight And Obesity ◽  
The Body ◽  
Breast Cancer Patients ◽  
Cancer Specific Survival ◽  
Er Positive ◽  
The Impact

Abstract Objective The relationship between the body mass index (BMI) at the time of breast cancer diagnosis and the prognosis of breast cancer patients has not yet been clarified. We investigated the impact of obesity for clinical outcomes in Japanese breast cancer patients. Methods Women with primary breast cancer operated between 2002 and 2014 were identified. All patients are categorized into four groups according to BMI. The range of BMI is <18.5 kg/m2, from 18.5 to 24.9 kg/m2, 25 to 29.9 kg/m2, >30 kg/m2 in underweight, normal, overweight and obesity groups, respectively. The correlation between BMI and overall survival (OS), breast cancer-specific survival (BCSS) and disease-free survival (DFS) were statistically analyzed. Results From the database of our institution, we identified 3223 patients. The median follow-up period was 57 months (1–149). We categorized 2257 (70.0%), 318 (9.9%), 545 (16.9%) and 103 (3.2%) patients into normal, underweight, overweight obesity groups respectively. There were189 patients (5.9%) deaths due to breast cancer recurrence (137 patients) and other disease (52 patients). Obesity groups was significantly high compared with normal groups for OS (adjusted HR, 2.43; 95% CI, 1.38–4.28; P < 0.001), BCSS (adjusted HR, 2.73; 95% CI, 1.15–6.44; P = 0.02) and DFS (adjusted HR, 1.83; 95% CI, 1.11–3.02; P = 0.017) by multivariate analysis. Especially, OS (adjusted HR, 4.87; 95% CI, 2.15–11.04; P < 0.001), BCSS (adjusted HR, 4.51; 95% CI, 1.52–13.34; P < 0.001) and DFS (adjusted HR, 4.87; 95% CI, 1.02–4.89; P = 0.04) were statistically insignificant in postmenopausal ER-positive breast cancer patients. Conclusion Obesity might be risk factor for OS, BCSS and DFS, especially postmenopausal ER-positive women.

scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Tumor Proliferation ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Secondary Outcomes ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.

scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Tumor Proliferation ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
Er Positive ◽  
Secondary Outcomes ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The influence of carbohydrates in breast cancer is conflicting.Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors.Design Randomized controlled trial.Setting University hospital with primary and secondary care functions in South-West Norway.Patients A population-based cohort of 61 patients with operable breast cancer.Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35).Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months).Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being.Limitation Only applicable to ER-positive breast cancer patients with T2-tumors.Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients.

scholarly journals Influence of pre-operative oral carbohydrate loading vs. standard fasting procedure on tumor proliferation and clinical outcome in breast cancer patients — a randomized trial

2019 ◽  
Author(s):  
Tone Hoel Lende ◽  
Marie Austdal ◽  
Anne Elin Varhaugvik ◽  
Ivar Skaland ◽  
Einar Gudlaugsson ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Well Being ◽  
Breast Cancer Patients ◽  
Relapse Free Survival ◽  
Free Survival ◽  
C Peptide ◽  
Er Positive ◽  
Carbohydrate Load ◽  
Per Oral

Abstract Background The influence of carbohydrates in breast cancer is conflicting. Objective To determine whether preoperative per-oral carbohydrate load influences proliferation in breast tumors. Design Randomized controlled trial. Setting University hospital with primary and secondary care functions in South-West Norway. Patients A population-based cohort of 61 patients with operable breast cancer. Intervention Per-oral carbohydrate load (preOp™) 18 and 2-4 hours before surgery (n=26) or standard pre-operative fasting procedure with free consume of tap water (n=35). Measurements Primary outcome was post-operative tumor proliferation measured as mitotic activity index (MAI). Secondary outcomes were changes in serum insulin, insulin-c-peptide, glucose, IGF-1 and IGFBP3. Other secondary outcomes were patients´ well-being and clinical outcome (median follow-up 88, range 33-97 months). Results In the estrogen receptor (ER) positive subgroup (n=50), high proliferation (MAI≥ 10) occurred more often in the carbohydrate group (CH) than in the fasting group (p=0.038). Progesterone receptor (PR) was more frequently negative in the CH-group (p=0.014). CH-patients had a significant between group rise in insulin (+ 24.31 mIE/L, 95% CI, 15.34 mIE/L to 33.27 mIE/L), insulin c-peptide (+ 1.39 nM, 95% CI, 1.03 nM to 1.77 nM), but reduced IGFBP3 levels (– 0.26 nM; 95% CI, ­– 0.46 nM to – 0.051 nM). CH-Intervention ER-positive patients had poorer relapse free survival (73%) than the fasting group (100%) (p=0.012; HR= 9.3 (95%CI, 1.1 to 77.7)). In the ER-positive patients, only tumor size (p=0.021; HR=6.07, 95%CI=1.31 to 28.03) and CH-or-fasting grouping (p=0.040; HR=9.30, 95% CI=1.11 to 77.82) had independent prognostic value. The adverse clinical outcome of carbohydrate loading occurred only in T2 patients with Relapse Free Survival of 100% in the fasting group vs. 33% in the CH-group (p=0.015; HR= inf). The CH-group reported less pain on day 5 and 6 compared to the control group (p<0.001) but showed otherwise no factors related to well-being. Limitation Only applicable to ER-positive breast cancer patients with T2-tumors. Conclusions Preoperative carbohydrate load increases proliferation and PR-negativity in ER-positive patients and worsens clinical outcome in ER-positive T2-patients. Keywords: breast cancer, carbohydrate load, proliferation, insulin, insulin c-peptide, IGF-1, IGFBP3, tumor size, relapse free survival, breast cancer specific survival

scholarly journals Clinical CYP2D6 Genotyping to Personalize Adjuvant Tamoxifen Treatment in ER-Positive Breast Cancer Patients: Current Status of a Controversy

Cancers ◽  
2021 ◽  
Vol 13 (4) ◽  
pp. 771
Author(s):  
Tessa A. M. Mulder ◽  
Mirjam de With ◽  
Marzia del Re ◽  
Romano Danesi ◽  
Ron H. J. Mathijssen ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Clinical Outcome ◽  
Cancer Patients ◽  
Plasma Concentrations ◽  
Tamoxifen Treatment ◽  
Current Status ◽  
Endocrine Treatment ◽  
Breast Cancer Patients ◽  
Er Positive ◽  
Positive Breast Cancer

Tamoxifen is a major option for adjuvant endocrine treatment in estrogen receptor (ER) positive breast cancer patients. The conversion of the prodrug tamoxifen into the most active metabolite endoxifen is mainly catalyzed by the enzyme cytochrome P450 2D6 (CYP2D6). Genetic variation in the CYP2D6 gene leads to altered enzyme activity, which influences endoxifen formation and thereby potentially therapy outcome. The association between genetically compromised CYP2D6 activity and low endoxifen plasma concentrations is generally accepted, and it was shown that tamoxifen dose increments in compromised patients resulted in higher endoxifen concentrations. However, the correlation between CYP2D6 genotype and clinical outcome is still under debate. This has led to genotype-based tamoxifen dosing recommendations by the Clinical Pharmacogenetic Implementation Consortium (CPIC) in 2018, whereas in 2019, the European Society of Medical Oncology (ESMO) discouraged the use of CYP2D6 genotyping in clinical practice for tamoxifen therapy. This paper describes the latest developments on CYP2D6 genotyping in relation to endoxifen plasma concentrations and tamoxifen-related clinical outcome. Therefore, we focused on Pharmacogenetic publications from 2018 (CPIC publication) to 2021 in order to shed a light on the current status of this debate.

Can Intratumoral neutrophil lymphocyte ratio (NLR) be a prognostic biomarker in breast cancer patients?

2021 ◽  
Vol 39 (15_suppl) ◽  
pp. e12573-e12573
Author(s):  
Yoshihisa Tokumaru ◽  
Masanori Oshi ◽  
Vijayashree Murthy ◽  
Eriko Katsuta ◽  
Nobuhisa Matsuhashi ◽  
...  
Keyword(s):  
Breast Cancer ◽  
T Cells ◽  
Cancer Patients ◽  
Immune Cells ◽  
Breast Cancer Patients ◽  
Immune Microenvironment ◽  
High Group ◽  
Anti Cancer ◽  
Tumor Immune Microenvironment ◽  
Er Positive

e12573 Background: In breast cancer patients, it is well known that the elevation of neutrophil lymphocyte ratio (NLR) in the blood are reported to associate with poor prognosis based on the notion that neutrophils represent pro-cancer, and lymphocytes represent anti-cancer immune cells. Tumor immune microenvironment has been demonstrated to play critical roles in the outcome of breast cancer patients. However, there is scarce evidence on the clinical relevance of intratumoral NLR in breast cancer patients. In the current study, we hypothesized that intratumoral NLR high tumors are associated with worse survival particularly in TNBC that is known to have high immune cell infiltration. Methods: A total of 1904 breast cancer patients’ data from METABRIC (Molecular Taxonomy of Breast Cancer International Consortium) and analyzed. NLR was calculated by the gene expressions of CD66b (CEACAM8) and CD8 (CD8A). NLR high and low were divided by the median. Overall Survival (OS) and Disease-Free Survival were calculated utilizing Kaplan Meier method between intratumoral NLR high and low groups. xCell algorithm was used to analyze the infiltrated immune cells within the tumor immune microenvironment as we have previously published. Results: Intratumoral NLR high group was associated with worse OS in whole, ER-positive/HER2-negative, and triple negative (TN) subtypes, in agreement with the previous studies. TN subtype alone demonstrated worse DFS of NLR high group. Surprisingly, gene set enrichment analysis (GSEA) demonstrated no gene set enrichment to NLR high group, which implicates that there is no distinctive mechanism that associate with worse survival. Whereas, immune response-related gene sets significantly enriched to NLR low group in TN subtype. This enrichment was consistent in ER-positive/HER2-negative. Compared with ER-positive/HER2-negative subtype, anti-cancer immune cells such as CD4+ T cells, CD8+ T cells, M1 macrophage, and helper T helper type 1 cells were significantly infiltrated in TN patients (p < 0.001 for all genes), where M2 macrophages and neutrophils were less and regulatory T cells and T helper type 2 cells were more infiltrated in TN subtype. Furthermore, intratumoral NLR was significantly lower in TN compared with ER-positive/HER2-negative subtype (p < 0.001). These results suggest that intratumoral NLR low group is associated with better survival due to favorable tumor immune microenvironment in TN subtype rather than NLR high group has worse survival. Conclusions: Intratumoral NLR low tumor demonstrated more favorable OS and more favorable DFS in TN patients. Intratumoral NLR low breast cancer was associated with enhanced immune response and higher infiltration of anti-cancer immune cells were observed in TN subtype compared to ER-positive/HER2-negative which may contribute to the favorable outcome of in TN breast cancer.

scholarly journals Analysis of ESR1 and PIK3CA mutations in plasma cell-free DNA from ER-positive breast cancer patients

Oncotarget ◽  
2017 ◽  
Vol 8 (32) ◽  
pp. 52142-52155 ◽  
Author(s):  
Takashi Takeshita ◽  
Yutaka Yamamoto ◽  
Mutsuko Yamamoto-Ibusuki ◽  
Mai Tomiguchi ◽  
Aiko Sueta ◽  
...  
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Plasma Cell ◽  
Breast Cancer Patients ◽  
Cell Free Dna ◽  
Pik3ca Mutations ◽  
Free Dna ◽  
Er Positive ◽  
Positive Breast Cancer

scholarly journals Risk of contralateral breast cancer according to first breast cancer characteristics among women in the USA, 1992–2016

2021 ◽  
Vol 23 (1) ◽  
Author(s):  
Cody Ramin ◽  
Diana R. Withrow ◽  
Brittny C. Davis Lynn ◽  
Gretchen L. Gierach ◽  
Amy Berrington de González
Keyword(s):  
Breast Cancer ◽  
Cancer Patients ◽  
Cumulative Incidence ◽  
Contralateral Breast Cancer ◽  
Breast Cancer Treatment ◽  
Contralateral Breast ◽  
Breast Cancer Patients ◽  
Younger Women ◽  
Er Positive

Abstract Background Estimates of contralateral breast cancer (CBC) risk in the modern treatment era by year of diagnosis and characteristics of the first breast cancer are needed to assess the impact of recent advances in breast cancer treatment and inform clinical decision making. Methods We examined CBC risk among 419,818 women (age 30–84 years) who were diagnosed with a first unilateral invasive breast cancer and survived ≥ 1 year in the US Surveillance, Epidemiology, and End Results program cancer registries from 1992 to 2015 (follow-up through 2016). CBC was defined as a second invasive breast cancer in the contralateral breast ≥ 12 months after the first breast cancer. We estimated standardized incidence ratios (SIRs) of CBC by year of diagnosis, age at diagnosis, and tumor characteristics for the first breast cancer. Cumulative incidence of CBC was calculated for women diagnosed with a first breast cancer in the recent treatment era (2004–2015, follow-up through 2016). Results Over a median follow-up of 8 years (range 1–25 years), 12,986 breast cancer patients developed CBC. Overall, breast cancer patients had approximately twice the risk of developing cancer in the contralateral breast when compared to that expected in the general population (SIR = 2.21, 95% CI = 2.17–2.25). SIRs for CBC declined by year of first diagnosis, irrespective of age at diagnosis and estrogen receptor (ER) status (p-trends < 0.001), but the strongest decline was after an ER-positive tumor. The 5-year cumulative incidence of CBC ranged from 1.01% (95% CI = 0.90–1.14%) in younger women (age < 50 years) with a first ER-positive tumor to 1.89% (95% CI = 1.61–2.21%) in younger women with a first ER-negative tumor. Conclusion Declines in CBC risk are consistent with continued advances in breast cancer treatment. The updated estimates of cumulative incidence inform breast cancer patients and clinicians on the risk of CBC and may help guide treatment decisions.

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