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Background <p>Family history is a well-established risk factor for breast cancer; however, its association with tumor characteristics and clinical outcomes remains unclear, particularly in Eastern Mediterranean populations. This study aimed to evaluate the relationship between family history and clinicopathologic features, disease-free survival, and distant metastasis in a large cohort of patients with breast cancer in Iran.</p> Methods <p>In this retrospective cohort study, 6115 women with pathologically confirmed breast cancer (1999–2024) were included. Family history was defined as a positive or negative history of breast cancer in first- or second-degree relatives. Logistic regression models were used to assess associations between family history and tumor characteristics at presentation. Multivariable Cox proportional hazards models were applied to evaluate disease-free survival. Models were adjusted for age, tumor stage, receptor status, proliferation index, and lymphovascular invasion. We handled missing data using multiple imputation.</p> Results <p>28.5% (1,745/6,115) of patients reported a positive family history. These patients were less likely to present with node-positive disease (adjusted odds ratio 0.76, 95% confidence interval 0.62–0.93; <i>P</i> = .006), while the association with advanced stage was not statistically significant after adjustment (adjusted odds ratio 0.81, 95% confidence interval 0.63–1.03; <i>P</i> = .09). No independent associations were observed between family history and proliferation index, lymphovascular invasion, distant metastasis, or disease-free survival (adjusted hazard ratio 0.93, 95% confidence interval 0.72–1.21; <i>P</i> = .59). High proliferation index and lymphovascular invasion were independently associated with worse disease-free survival.</p> Conclusions <p>Family history was associated with lower nodal involvement at diagnosis but was not independently associated with tumor biology or clinical outcomes. These findings suggest that family history appears to be more strongly associated with breast cancer risk rather than disease progression and may reflect earlier detection rather than differences in tumor aggressiveness.</p>

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Family history and stage at diagnosis but not prognosis in female breast cancer: a large registry-based cohort study from Iran

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2026年8月5日

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  • Shapour Azizi,
  • Zahra Hosseinpour,
  • Atieh Akbari,
  • Mohammad-Esmaeil Akbari

摘要

Background

Family history is a well-established risk factor for breast cancer; however, its association with tumor characteristics and clinical outcomes remains unclear, particularly in Eastern Mediterranean populations. This study aimed to evaluate the relationship between family history and clinicopathologic features, disease-free survival, and distant metastasis in a large cohort of patients with breast cancer in Iran.

Methods

In this retrospective cohort study, 6115 women with pathologically confirmed breast cancer (1999–2024) were included. Family history was defined as a positive or negative history of breast cancer in first- or second-degree relatives. Logistic regression models were used to assess associations between family history and tumor characteristics at presentation. Multivariable Cox proportional hazards models were applied to evaluate disease-free survival. Models were adjusted for age, tumor stage, receptor status, proliferation index, and lymphovascular invasion. We handled missing data using multiple imputation.

Results

28.5% (1,745/6,115) of patients reported a positive family history. These patients were less likely to present with node-positive disease (adjusted odds ratio 0.76, 95% confidence interval 0.62–0.93; P = .006), while the association with advanced stage was not statistically significant after adjustment (adjusted odds ratio 0.81, 95% confidence interval 0.63–1.03; P = .09). No independent associations were observed between family history and proliferation index, lymphovascular invasion, distant metastasis, or disease-free survival (adjusted hazard ratio 0.93, 95% confidence interval 0.72–1.21; P = .59). High proliferation index and lymphovascular invasion were independently associated with worse disease-free survival.

Conclusions

Family history was associated with lower nodal involvement at diagnosis but was not independently associated with tumor biology or clinical outcomes. These findings suggest that family history appears to be more strongly associated with breast cancer risk rather than disease progression and may reflect earlier detection rather than differences in tumor aggressiveness.