From: Environmental chemicals, breast cancer progression and drug resistance
Year/Country | Studies (ref) | Study design | Study population (percentage premenopausal) | Type of chemicals investigated | Measurment of exposure | Time at measurement | Outcome(s) | Results - hazard ratios | Conclusion/Comments |
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2000 Danemark | [69] | Cohort | 195 women with breast cancer | Organochlorines | Serum Dieldrin HCB DDE, DDT and their metabolites 27 PCB (28, 42, 66, 74, 99, 101, 105, 110, 118, 138,146, 153, 156, 170, 172, 177, 178, 180, 183, 187, 189, 193,194, 195, 201, 203, and 206) | At diagnosis; from 1976 to 1978 | Association DDT and DDE levels and breast cancer survival | Dieldrin exposure was associated with a decrease overall survival OR = 4.6 (95% CI = 1.8–11.5) | Exposure to estrogenic organochlorines such as dieldrin may affect breast cancer survival |
2000 Canada | [58] | Case control | 315 women newly diagnosed with breast cancer 307 controls | Organochlorines | Serum 14 PCB congeners (28,52,99,101,105,118,128,138,153,156,170,180,183,187) 11 chrorinated pesticides or their metabolites (aldrin, α-chlordane, γ-chlordane, p,p′-DDT, p,p′-DDE, hexachlorobenzene, β-HCH, mirex, cis-nonachlor, trans-nonachlor, oxychlordane) | At diagnosis; from 1994 to 1997 | Association between organochlorine concentrations and tumor size and axillary lymph node involvement | ↑ risk of lymph node involvement with exposure to p,p′-DDE OR = 2.54 (95% CI = 1.20–5.35) (comparison between highest and lowest tertiles) Dose related increased risk for DDE and large tumors withlymph node involvement Associations between tumor size and lymph-node involvement for betaHCH, oxychlordane, and trans-nonachlor ↑ risk of lymph node involvement with PCB 153 (chosen as a surrogate for all the highly prevalent PCBs) OR = 2.12 (95% CI = 1.5–4.30) No interaction between organochlorine exposure and the hormonal status of the tumor with regard to either axillary-lymph-node involvement or tumor size (204 patients) | p,p’-DDE and PCB 153 exposure could be associated with a more aggressive breast cancer phenotype regardless of ER status |
2001 USA | [80] | Case control | 88 women with unilateral invasive breast cancer and pulmonary metastatic disease matched with 176 controls patients without metastatic disease | Tabacco smoke | Smoking “dose” not available No chemicals measured | At diagnosis; no information about period | Association between cigarette smoking and the development of pulmonary metastatic disease | −24.1% in case patients active smokers vs 15.3% in control Unadjusted OR = 1.76 (no IC), p = 0,06 -Multivariate analysis including hormonal therapy and presence of other metastatic sites: OR = 1,96 (95%IC = 0.96–4.02), p = 0.06 | Cigarette smoking could increase pulmonary metastatic disease risk |
2001 Danemark | [59] | Case control | 240 women with breast cancer and 477 controls | Organochlorines | Dieldrin HCB 27 PCB (28, 42, 66, 74, 99, 101, 105, 110, 118, 138,146, 153, 156, 170, 172, 177, 178, 180, 183, 187, 189, 193,194, 195, 201, 203, and 206) | At diagnosis; from 1976 to 1978 | Association between organochlorine concentrations and breast cancer risk and survival according to estrogen receptor status | Sum of PCB was significantly associated with risk of death among women with ER+ tumors OR = 2.5 (95%CI = 1.1–5.7) Dieldrin exposure was associated with elevated mortality among women with ER+ tumors | Suggests a link between PCB & dieldrin exposure and ER tumors progression |
2002 Canada | [60] | Case control | 314 women with breast cancer and 523 controls | Polychlorinated biphenyls | Serum 14 PCB (28, 52, 99, 101, 105, 118, 128, 138, 153, 156, 170, 180, 183 and 187) | At diagnosis; from 1994 to 1996 | Association between PCB exposure and breast cancer risk | No association was found between PCB congeners and both tumor size and lymph node involvement | N/A |
2003 USA | [61] | Cohort | 224 women with nonmetastatic breast cancer | Organochlorines | Serum and adipose tissue 7 pesticides including DDE and DDT DDE trans-nonachlor, oxychlordane, β-HCH) 14 PCB (74, 99, 118, 138, 146, 153, 156, 167, 170, 172, 178, 180, 183, 187) | At diagnosis; from 1994 to 1996 | Association between organochlorine concentrations and breast cancer recurrence | Total PCB levels were associated with an increased risk of breast cancer recurrence OR = 2.9, 95% CI = 1.02–8.2) (comparison between highest and lowest tertiles) Higher risk for PCB 118 OR = 4.0 (95% CI, 1.3–4.9) ORs for most PCB congeners were elevated, ORs > 2 for 118, 138, 153, 167, 183, and 187. Association DDT and DDE levels and breast cancer recurrence Statistically unstable elevated risk of recurrence associated with HCB, β-HCH, and trans-nonachlor | PCB, DDT and DDE exposure could be associated with cancer recurrence |
2012 Brasil | [93] | Case control | 81 women 38 controls, 9 benign tumors (fibroadenoma) and 34 breast cancer (both in situ and infiltrating ductal carcinomas) Total of 106 samples of breast tissue (34 from premonopausal patient) Medical record available for 57 patients | Trace element | Breast tissue total amount of Iron (Fe), Copper (Cu), Calcium (Ca) and Zinc (Zn) + Amount 2 cm away from the tumor (benign and malignant tumor) | At diagnosis; from 2003 to 2006 | Overall survival | Patients with positive expression for Cu presented a poor overall survival (p < 0.001) | Exposure to copper could be associated with a decreased overall survival of breast cancer patients |
2016 USA | [68] | Cohort | 633 women with a first primary invasive or in situ breast cancer (66% postmenopausal) | Organochlorines | Serum DDT, DDE and chlordane | At diagnosis; from 1996 to 1997 | Association between organochlorine concentration and overall and breast cancer-specific 5-year and 15-year mortality | −5-year overall mortality (comparison between highest and tertiles 2 and 3) DDT HR = 2.19 (95% CI = 1.02, 4.67) − 5-year breast cancer-specific mortality HR = 2.72 (95% CI = 1.04, 7.13) - At 15 years, concentrations of DDT and chlordane were modestly associated with overall and breast cancer-specific mortality (HR = 1.42 (95% CI =0.99, 2.06) and HR = 1.42 (95% CI = 0.94, 2.12) respectively) | DDT concentration was associated with all-cause and breast cancer-specific mortality |
2016 USA | [63] | Cohort | 627 women with a first primary invasive or in situ breast cancer | Polychlorinated biphenyls | Serum 22 PCB individually and by estrogenic group (101, 174, 177, 187, 199), antiestrogenic group (66, 74, 105, 118, 138, 170) and cytochrome P450 enzyme inducing group (99, 153, 180, 183, 203) | At diagnosis; from 1996 to 1997 | Association between polychlorinated biphenyls concentration and overall and breast cancer-specific 5-year and 15-year mortality | −5-year overall mortality (comparison between highest and tertiles 2 and 3) PCB 174 HR = 2.22 (95% CI = 1.14–4.30) PCB177 HR = 2.12 (95% CI = 1.05–4.30) − 5-year breast cancer-specific mortality HR = 3.15 (95% CI = 1.23–8.09) −15-year breast cancer-specific mortality PCB 174 HR = 1.88 (95% CI = 1.05–3.36) PCB118 and antiestrogenic group inversely associated with overall mortality HR = 0.60 (95% CI = 0.39–0.83 and HR = 0.63 (95% CI = 0.43–0.92) respectively | See left column |
2016 Spain | [62] | Cohort | 103 women newly diagnosed with breast cancer (40.8% postmenopausal) | Organochlorines | Serum and adipose tissue p,p’-DDE, HCB PCB 138 PCB 153 PCB 180 | From 2012 to 2014 | Association between exposure to a group of organochlorines and tumor prognostic markers | HCB levels were associated with: -ER and PR expression (p-trends = 0.044 and 0.005, respectively) -decreased E-Cadherin expression (p-trends = 0.012) and p53 expression (p-trends = 0.027) PCB 180 adipose tissue levels were associated with HER2 expression (p-trend = 0.036) PCB 138 Serum were associated with - ER and PR expression (p-trends = 0.052 and 0.042, respectively) | Exposure to certain persistent organic pollutants (HCB, PCB 138 & 180) might be related to breast cancer aggressiveness |
2017 Ukraine | [92] | Case control | 40 samples of breast cancer tissue and 20 samples of intact breast tissue | Toxic metals | Breast tissue total amount of Iron (Fe), Copper (Cu), Zinc (Zn), Lead (Pb), Chromium (Cr) and Nickel (Ni) | At diagnosis | Link between chemical composition of neoplasic breast tissue and DNA methylation level, O6-methyguanine-DNA methyltransferase levels and prognostic-important receptors expression | The growth of toxic metals in neoplastic tissue is accompanied with: ↑ HER2/neu (r = 0.36, p < 0.05) ↑ p53 (r = 0.53, p < 0.01) ↑ Ki-67 (r = 0.47, p < 0.01) ↑ O6-methyguanine-DNA methyltransferase (r = 0.34, p < 0.05) ↓ ER (r = − 0.71, p < 0.01) ↓ PR (r = − 0.66, p < 0.01) ↑ pathological DNA methylation in tumor tissue (r = 0.41, p < 0.01) | Several toxic metals could stimulate the progression of breast cancer and reduce its sensitivity to treatment |
2019 USA | [70] | Case control | 456 white and 292 black women with breast cancer | Organochlorines | Serum lipid-standardized DDT and DDE levels | 4.1 months after diagnosis; patient included from 1993 to 1996 | Breast cancer-specific 5-year mortality Overall 20-year mortality conditional on 5-year survival | −20-year conditional overall mortality 1/ DDE: HR =1.95 (95% CI = 1.31–2.92) (comparison between highest versus lowest DDE tertile) 2/DDT: HR = 1.64 (95% CI = 1.10–2.44) (comparison highest vs undetectable DDT quantile) - 20-year conditional breast cancer-specific mortality 1/DDE: comparison levels above versus below the median) Among women overall: HR = 1.69 (95% CI = 1.06–2.68) Among black women: HRs =2.36 (95% CI = 1.03–5.42) Among white women: OR = 1.57 (95% CI = 0.86–2.89) (PInteraction = 0.42). Among women with ER- tumors: OR = 3.24 (95% CI = 1.38–7.58) Among women with ER+ tumors: OR = 1.29 (95% CI = 0.73–2.28) (PInteraction = 0.03). | Exposure to DDE/DDT may impact overall and breast cancer-specific survival |
2019 France | [56] | Case control | 91 women newly diagnosed with breast cancer 53 nonmetastatic and 38 metastatic (lymph node involvement) | 49 persistent organic pollutants including PCB, PBDE, PBB and HBCD | Serum and adipose peritumoral tissue | At diagnosis; 2013–2017 | Association between pollutants concentrations and lymph node involvement | 2.3.7.8-TCDD concentrations in adipose tissue are associated with the risk of lymph node metastasis in patients with BMIs equal or higher than 25 kg/m2 OR = 4.48 (95%CI = 1.32–20.71) 2.3.7.8-TCDD concentrations and PCB 77 and 169 in adipose tissue are associated with risk of lymph node metastasis and tumor size | 2.3.7.8-TCDD could contribute to the development of tumor metastasis in overweight patients |