In this contribution, different measurement noise pre-filtering techniques were developed using frequency-domain fluorescence measurements of homogeneous breast phantoms. We demonstrated that implementing noise pre-filtering, based on modulation depth and measurement error in amplitude, can improve model match between experimental and simulated data under varying experimental conditions (target depths, 1-3 cm and fluorescence optical contrast, 1:0 and 100:1). Noise pre-filtering also improves the qualitative estimation of target(s) location in reconstructed images in deep target(s) when there was fluorescence in the background. Interestingly, decreases in model mismatch did not necessarily correlate with increases in reconstructed target accuracy. In addition, it was observed that pre-filtering measurement noise using different criteria can help differentiate target(s) from artifacts, thus possibly minimizing the false-positive cases in a clinical environment.