A claim you hear on longevity podcasts

Does high insulin raise breast cancer risk?

Leaning for. Of 9 studies that test it, 5 agree, 3 partly agree and 1 disagrees.

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Women with insulin resistance who want to know about breast cancer
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The claim checked: High insulin makes cancer cells grow Hear it at 6:12

What do the studies say?

Leaning for

Five of nine studies agree. In the Women's Health Initiative, women past menopause with high insulin had a higher risk of breast cancer, even after body weight was counted. A genetic study found risk rose about 70% for each step up in fasting insulin. One disagrees: in mostly younger women, high insulin was not a real risk factor. Three are mixed. A pooled analysis of 22 studies found no link with fasting insulin, though C-peptide, a marker of how much insulin the body makes, was linked.

Computed from 9 studies that test this point, each judged by two readers, in full. 10 more studies are waiting for a full read and do not count yet.

What was said on the podcast?

“We know that high levels of insulin in the body really create growth of cancer cells. So, we're always evaluating, does this person have high levels of insulin? Do they have insulin resistance?”
Elizabeth Boham, a guest on The Doctor's Farmacy · It's Not Bad Luck. This Is What Actually Makes Your Body Vulnerable to Breast Cancer · 6:12 on YouTube
Episode check Bioidentical hormone therapy does not cause breast cancer, the episode says. Four studies conflict on it. 6 claims checked against 72 studies · 7 chapters not checked yet See the whole episode →
Point 1 of 2 Leaning for

Women with high insulin levels or insulin resistance have a higher risk of breast cancer

Agree 5

other primary study · 2009 · landmark

“These data suggest that hyperinsulinemia is an independent risk factor for breast cancer and may have a substantial role in explaining the obesity–breast cancer relationship.”

Insulin, insulin-like growth factor-I, and risk of breast cancer in postmenopausal women. J Natl Cancer Inst
Who: nondiabetic postmenopausal women aged 50-79 in the Women's Health Initiative Observational Study (case-cohort: 835 incident breast cancer cases and a random subcohort of 816)
PMID 19116382

other primary study · 2015

“Our findings also support the hypothesis that hyperinsulinemia is a significant risk factor for breast cancer, independent of adiposity and that insulin, or a closely-related mechanism, may be driving development of breast tumors.”

Breast cancer risk in metabolically healthy but overweight postmenopausal women. Cancer Res
Who: nondiabetic postmenopausal women aged 50-79 not using hormone therapy, from two Women's Health Initiative studies (observational and clinical trial components) with fasting insulin and glucose
PMID 25593034

other primary study · 2019

“We found that the risk of breast cancer increased approximately 70% for each SD increase of genetically predicted fasting insulin levels.”

Associations of obesity and circulating insulin and glucose with breast cancer risk: a Mendelian randomization analysis. Int J Epidemiol
Who: women of European descent in the Breast Cancer Association Consortium (98,842 breast cancer cases and 83,464 controls); genetic instruments validated in the DIAGRAM type 2 diabetes consortium
PMID 30277539

other primary study · 2013

“49% of cases were insulin resistant respect to 34% of controls [OR 1.86], suggesting that insulin resistance can nearly double the risk of breast cancer development.”

Homeostasis model assessment to detect insulin resistance and identify patients at high risk of breast cancer development: National Cancer Institute of Naples experience. J Exp Clin Cancer Res
Who: 975 non-diabetic Italian women aged 35-75 at the National Cancer Institute of Naples, 2008-2011: 410 operated for breast cancer and 565 healthy screening controls
PMID 23497533

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other primary study · 2013

“However, c-peptide was associated with an approximately 50% increased risk of invasive breast cancer (top vs. bottom quartile, adjusted OR=1.5, 95% CI: 1.1, 2.0) that was robust to adjustment for plasma free estradiol and SHBG.”

Plasma C-peptide, mammographic breast density, and risk of invasive breast cancer. Cancer Epidemiol Biomarkers Prev
Who: nested case-control studies within the Nurses' Health Study (blood 1989-1990) and Nurses' Health Study II (blood 1996-1999), US female registered nurses, pre- and postmenopausal
PMID 24097198

Partly agree 3

pooled analysis · 2014

“In observational studies, higher levels of fasting insulin or non-fasting/fasting C-peptide were not found to be associated with the presence of breast cancer in women, even after adjustment for important confounders.”

Association between insulin resistance and breast carcinoma: a systematic review and meta-analysis. PLoS One
Who: women aged >=18 with and without breast cancer in 22 observational studies (20 case-control, 2 cross-sectional) measuring fasting insulin, C-peptide or HOMA-IR
PMID 24911052

other primary study · 2019

“C-peptide was the only metabolic hormone significantly associated with breast cancer risk.”

Metabolic hormones and breast cancer risk among Mexican American Women in the Mano a Mano Cohort Study. Sci Rep
Who: Mexican American women in the Mano a Mano Cohort Study (Houston, Texas); nested case-control of 109 incident breast cancer cases and 327 healthy controls
PMID 31292496

systematic review · 2020

“The current meta-analysis suggests that C-peptide levels were positively related to breast cancer risk in women, and no relationship between insulin and breast cancer was found.”

Association Between Serum Insulin and C-Peptide Levels and Breast Cancer: An Updated Systematic Review and Meta-Analysis. Front Oncol
Who: women newly diagnosed with breast cancer before treatment and controls without breast cancer, from case-control, nested case-control and cohort studies with fasting blood
PMID 33194614

Disagree 1

other primary study · 2007

“Thus, high levels of insulin and c-peptide do not seem to be substantial risk factors for breast cancer among predominantly premenopausal women.”

Circulating insulin and c-peptide levels and risk of breast cancer among predominately premenopausal women. Cancer Epidemiol Biomarkers Prev
Who: nested case-control study in the Nurses' Health Study II: cancer-free women aged 32-54 at blood collection (1996-1999), 75% premenopausal
PMID 17220346

Point 2 of 2 Leaning for

In women with breast cancer, high insulin levels go with more cancer growth (recurrence or death)

Three of six studies agree. In 604 women with breast cancer, each 1 ng/mL rise in C-peptide went with a 35% higher risk of dying of breast cancer. In Rome, an insulin level above 13 went with more than twice the risk of the cancer progressing. Three are mixed: in some, the link depended on the type of tumour, or was too uncertain to count.

Computed from 6 studies that test this point, each judged by two readers, in full. 5 more studies are waiting for a full read and do not count yet.

Agree 3

other primary study · 2011

“Our study confirms the importance of hyperinsulinemia as an independent risk factor for poor prognosis in women with breast cancer and the association between low levels of adiponectin and shorter breast cancer survival.”

Associations of insulin resistance and adiponectin with mortality in women with breast cancer. J Clin Oncol
Who: 527 women with stage I-IIIA breast cancer in the multiethnic HEAL Study (Seattle, New Mexico, Los Angeles), blood drawn about 30 months post-diagnosis
PMID 21115858

other primary study · 2011

“A 1-ng/mL increase in C-peptide was associated with a 31% increased risk of any death (HR = 1.31; 95% CI, 1.06 to 1.63; P = .013) and a 35% increased risk of death as a result of breast cancer (HR = 1.35; 95% CI, 1.02 to 1.87, P = .048).”

Fasting C-peptide levels and death resulting from all causes and breast cancer: the health, eating, activity, and lifestyle study. J Clin Oncol
Who: 604 women diagnosed with local or regional (stage I-IIIa) breast cancer in 1995-1998 in the multiethnic HEAL Study (New Mexico, Los Angeles County, Western Washington); 546 without type 2 diabetes
PMID 21115859

other primary study · 2016

“These results were largely unmodified after adjustment for other variables known to be associated with PFS, including disease stage, hormone receptor and HER2/neu status, and Ki67 proliferation index (HR for insulin levels >13 μIU/mL: 2.17; 95% CI: 1.13–4.20; overall model fit: p < .0001) (Table 4).”

Pretreatment Insulin Levels as a Prognostic Factor for Breast Cancer Progression. Oncologist
Who: 286 nondiabetic breast cancer patients (249 primary, 37 relapsing/metastatic) in Rome, Italy, plus 143 matched healthy control women
PMID 27388232

Partly agree 3

other primary study · 2011

“HOMA-IR and insulin values showed opposing effects according to ER/PR status.”

Adipokines, insulin resistance, metabolic syndrome, and breast cancer recurrence: a cohort study. Breast Cancer Res
Who: 747 newly diagnosed, surgically treated breast cancer patients (non-metastatic, mean age 45.9) at the National Cancer Center Hospital, Korea, 2001-2004
PMID 21450081

trial or observed group · 2020

“Insulin resistance (HOMA-IR) was positively associated with NPI scores ( r = 0.1; p = 0.02).”

Insulin resistance contributes to racial disparities in breast cancer prognosis in US women. Breast Cancer Res
Who: 515 women aged 21+ with newly diagnosed primary invasive breast cancer (428 non-Hispanic White, 87 Black) at ten US hospital sites in five states, excluding medication-treated diabetes
PMID 32393319

other primary study · 2025

“This association appeared to be partly explained by a potential reduction in BCSM, although this latter finding requires cautious interpretation due to its statistical imprecision and warrants validation in larger studies.”

Association of estimated glucose disposal rate with all-cause and breast cancer-specific mortality in US breast cancer survivors: a population-based study. BMC Cancer
Who: 323 US women aged 20+ with a self-reported prior breast cancer diagnosis in NHANES 2007-2016 (within 11,725 adult women analysed for prevalence)
PMID 41310487

Disagree 0· none of the studies we read

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