Local aromatase activity alterations in breast cancer tissues: A potential way of decision support for clinicians

Exp Mol Pathol. 2021 Feb:118:104574. doi: 10.1016/j.yexmp.2020.104574. Epub 2020 Nov 13.

Abstract

Background and aims: It is becoming evident that local estrogen exposure is important in postmenopausal breast cancer patients. The microenvironment is established by breast stromal cells based on communication with tumor cells that is essential to cancer development, invasion, and metastasis. Here we investigated aromatase activity levels in both tumor and matched stromal tissues by showing their impact on the manufacturing of local estrogen and tumor progression in cases of invasive ductal carcinoma (IDC).

Methods: Tumor (T) and tumor-associated stroma (TAS) neighboring tissues were acquired from each postmenopausal patient, diagnosed with IDC, and categorized as luminal A (n = 20). The control group was formed from tumor-free breast tissue samples (N, n = 12). A microsomal-based technique was created to compare breast tissue aromatase activities using liquid chromatography - mass spectrometry.

Findings: We observed that the TAS tissues have the highest aromatase activities (p < 0.05). High progesterone receptor (PR) intensity levels were found to be decreasing the activity level in these tissues significantly (p < 0.05). Tumor tissue specific aromatase activity levels of postmenopausal patients' were tend to be lower compared to healthy premenopausal subjects' (3 fold, p < 0.001). In addition low activity in tumor tissues were associated with low grade and late stage cancers.

Conclusions: Early detection and personalized therapy is essential for postmenopausal breast cancer patients. Together, our in-house tandem mass spectrometry technique has the potential for further development and standardization for the measurement of aromatase activity and may assist clinicians decide on therapy policies for postmenopausal IDC patients which could be an invaluable asset for precise and specific evaluation.

Keywords: Aromatase; Breast cancer; Estrogens; Mass spectrometry; Tumor microenvironment.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aromatase / metabolism*
  • Biomarkers, Tumor / metabolism
  • Breast Neoplasms / enzymology
  • Breast Neoplasms / pathology*
  • Breast Neoplasms / surgery
  • Carcinoma, Ductal, Breast / enzymology
  • Carcinoma, Ductal, Breast / pathology*
  • Carcinoma, Ductal, Breast / surgery
  • Case-Control Studies
  • Decision Making*
  • Female
  • Follow-Up Studies
  • Gene Expression Regulation, Enzymologic*
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Middle Aged
  • Precision Medicine
  • Prognosis
  • Receptors, Estrogen / metabolism
  • Receptors, Progesterone / metabolism
  • Stromal Cells / enzymology
  • Stromal Cells / pathology*
  • Tumor Microenvironment

Substances

  • Biomarkers, Tumor
  • Receptors, Estrogen
  • Receptors, Progesterone
  • Aromatase
  • CYP19A1 protein, human