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Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to risk of different breast cancer subgroups: a Malmö Diet and Cancer Study

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Abstract

Purpose

Thyroid hormone level has been positively associated with breast cancer risk and with breast cancer cell proliferation and growth. Although breast cancer is a heterogeneous disease, this is the first study assessing pre-diagnostic levels of free triiodothyronine (fT3), free thyroxine (fT4), thyroid-stimulating hormone (TSH), and thyroid peroxidase antibodies (TPO-Ab) in relation to breast cancer subgroups and aggressiveness.

Methods

The Malmö Diet and Cancer Study collected blood samples from 17,035 women between 1991 and 1996. Free T3, free T4, TSH, and TPO-Ab were analyzed in 676 incident breast cancer cases and 680 controls. Breast tumors were classified according to tumor size, axillary lymph node involvement, histological grade, histological type, hormone receptor status (ER, PgR), as well as Ki67, cyclin D1, and p27. Odds ratios of different breast cancer subgroups were calculated using a logistic regression analysis adjusted for potential confounders.

Results

High fT4 was associated with a statistically significant higher risk of overall breast cancer, small, grade I, ER-positive, PgR-positive, and cyclin D1 low tumors. The associations for ER and PgR were verified in a heterogeneity analysis. Low TPO-Ab was associated with a higher risk of overall breast cancer, ductal, large, ER-positive, PgR-positive, cyclin D1 low, and p27 high tumors. The heterogeneity analysis verified the association for tumor size. Free T3 was not associated with overall breast cancer risk, but in the heterogeneity analysis, high fT3 was associated with tumor size and expression of p27. There were no strong associations between TSH and overall breast cancer risk or any tumor subgroup.

Conclusion

High pre-diagnostic fT4 levels and low pre-diagnostic TPO-Ab levels were associated with an increased risk of breast cancer. This increase was mainly limited to a higher incidence rate of less aggressive breast cancer subgroups.

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Abbreviations

ALNI:

Axillary lymph node involvement

CI:

Confidence intervals

CIS:

Cancer in situ

ER:

Estrogen receptor

fT3:

Free triiodothyronine

fT4:

Free thyroxine

HRT:

Hormone replacement therapy

IHC:

Immunohistochemistry

MDCS:

The Malmö Diet and Cancer Study

PgR:

Progesterone receptor

SEI:

Socioeconomic index

TMA:

Tissue microarray

TPO-Ab:

Thyroid peroxidase antibodies

TSH:

Thyroid-stimulating hormone

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Acknowledgments

The authors would like to thank R.N. Anna Hwasser for excellent database management, Ms Elise Nilsson for skillful technical assistance, and Dr. Lola Anagnostaki for pathological re-evaluation. This work was supported by the Swedish Cancer Society, the Gunnar Nilsson Cancer Foundation, the Ernhold Lundström Foundation, the Einar and Inga Nilsson Foundation, the Malmö University Hospital Cancer Research Fund, the Skåne University Hospital Funds and Donations, the Breast Cancer network at Lund University (BCLU), and the Region Skåne (ALF).

Conflict of interest

The authors declare that they have no conflict of interest.

Author information

Authors and Affiliations

  1. Department of Surgery, Skåne University Hospital, Lund University, 205 02, Malmö, Sweden

    Jasmine Brandt & Jonas Manjer

  2. Department of Plastic Surgery, Skåne University Hospital, Lund University, Malmö, Sweden

    Jasmine Brandt & Jonas Manjer

  3. Division of Oncology and Pathology, Department of Clinical Sciences, Lund University, Lund, Sweden

    Signe Borgquist

  4. Department of Oncology, Skåne University Hospital, Lund, Sweden

    Signe Borgquist

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  1. Jasmine Brandt
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Correspondence to Jasmine Brandt.

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Brandt, J., Borgquist, S. & Manjer, J. Prospectively measured thyroid hormones and thyroid peroxidase antibodies in relation to risk of different breast cancer subgroups: a Malmö Diet and Cancer Study. Cancer Causes Control 26, 1093–1104 (2015). https://doi.org/10.1007/s10552-015-0602-8

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