Key Biophysical and Physiological Properties Impacting the Oxygenation Status of Breast Cancers During Thermo-radiotherapy.

Mild hyperthermia at 39-43 °C for 30-60 min is applied locoregionally to improve the oxygenation status of recurrent breast cancers, thus enhancing the efficacy of radio-, chemo-, and immunotherapy. In this context, estimated (or even conflicting) data are often used in computational modelling of tumour oxygenation and simulation of O₂ transport. In this chapter, we present information that may help to improve adjuvant thermotherapy delivered immediately prior to radiotherapy of recurrent breast cancers. Data are preferentially derived from clinical investigations; in some cases, measurements in experimental breast cancers are included.The biophysical properties presented for healthy, mostly postmenopausal, human breast (composite glandular-adipose-fibrous tissue) measured under normothermic (NT) conditions and in therapeutically heated breast cancers include tissue water content and tissue density. In general, averaged values of parameters reported for NT conditions are higher in breast cancers than in normal breast tissue, i.e., all ratios breast cancer/normal breast are >1. Mean values observed in breast cancers during mild hyperthermia (mHT) are consistently higher than those in NT tumours. Parameters determining convective transports in healthy breast tissue and breast cancer include blood flow rates, blood volume, exchanging water space, arterio-venous shunt flow, interstitial fluid flow rate, interstitial fluid pressure, microvascular permeability, interstitial hydraulic conductivity, and interstitial flow velocity. In general, averaged values of parameters measured under NT conditions are higher in breast cancers than in healthy breast. Except for interstitial fluid pressure, these values increase upon mHT treatment of cancers. Prime factors determining and describing the oxygenation status of the healthy breast, and in NT- versus mHT-treated breast cancers, include: oxygen (O₂) delivery rates, O₂- extractions, O₂- consumption rates, subepidermal microvascular HbO₂, tissue oxygen solubility, oxygen diffusion coefficients, mean O₂ partial pressures pO₂, hypoxic fractions HF <5 mmHg, oxygen enhancement ratio, and mitochondrial ROS production. With the exception of the mean pO₂, O₂ extraction rate and tissue O₂ saturation all parameters listed are distinctly higher in breast cancers under NT conditions compared to normal breast. Mild hyperthermia results in therapeutically relevant improvements of the oxygenation status of cancers and enhances mitochondrial ROS production, thus improving radiosensitivity. Note: The oxygenation status of the healthy (postmenopausal) breast is very similar to that of the normal human subcutis.