Breast cancer: assessing response to neoadjuvant chemotherapy by using US-guided near-infrared tomography

Abstract

Purpose: To assess initial breast tumor hemoglobin (Hb) content before the initiation of neoadjuvant chemotherapy, monitor the Hb changes at the end of each treatment cycle, and correlate these findings with tumor pathologic response.

Materials and methods: The HIPAA-compliant study protocol was approved by the institutional review boards of both institutions. Written informed consent was obtained from all patients. Patients who were eligible for neoadjuvant chemotherapy were recruited between December 2007 and May 2011, and their tumor Hb content was assessed by using a near-infrared imager coupled with an ultrasonography (US) system. Thirty-two women (mean age, 48 years; range, 32-82 years) were imaged before treatment, at the end of every treatment cycle, and before definitive surgery. The patients were graded in terms of their final pathologic response on the basis of the Miller-Payne system as nonresponders and partial responders (grades 1-3) and near-complete and complete responders (grades 4 and 5). Tumor vascularity was assessed from total Hb (tHb), oxygenated Hb (oxyHb), and deoxygenated Hb (deoxyHb) concentrations. Tumor vascularity changes during treatment were assessed from percentage tHb normalized to the pretreatment level. A two-sample two-sided t test was used to calculate the P value and to evaluate statistical significance between groups. Bonferroni-Holm correction was applied to obtain the corrected P value for multiple comparisons.

Results: There were 20 Miller-Payne grade 1-3 tumors and 14 grade 4 or 5 tumors. Mean maximum pretreatment tHb, oxyHb, and deoxyHb levels were significantly higher in grade 4 and 5 tumors than in grade 1-3 tumors (P = .005, P = .008, and P = .017, respectively). The mean percentage tHb changes were significantly higher in grade 4 or 5 tumors than in grade 1-3 tumors at the end of treatment cycles 1-3 (P = .009 and corrected P = .009, P = .002 and corrected P = .004, and P < .001 and corrected P < .001, respectively).

Discussion: These findings indicate that initial tumor Hb content is a strong predictor of final pathologic response. Additionally, the tHb changes during early treatment cycles can further predict final pathologic response.

Figure 1:

Box-and-whisker plot shows mean maximum tHb in micromoles per liter in Miller-Payne (MP) grade 1–3 tumors and grade 4 or 5 tumors before treatment (cycle 0) and at the ends of chemotherapy cycles 1–3.

Figure 2:

Scatterplot shows pretreatment maximum tHb in micromoles per liter for three types of tumors in two responder groups. MP = Miller-Payne.

Figure 3:

Box-and-whisker plot shows percentage tHb in grade 1–3 and grade 4 or 5 tumors before treatment (cycle 0) and at the ends of chemotherapy cycles 1–3. MP = Miller-Payne, Pc* = Bonferroni-Holm corrected P value (originally calculated with two-sample, two-sided t test).

Figure 4a:

Pathologic complete response in an HER2-positive tumor. Images in 55-year-old woman with intermediate-grade IDC treated with docetaxel and carboplatin with trastuzumab acquired (a, c, e) before treatment and (b, d, f) prior to surgery. (a, b) Sonograms show ill-defined heterogeneous tumor (arrows), which was palpable at the beginning of the treatment. (c, d) Maps of tHb concentration show spatial distribution of tHb concentration reconstructed from 0.5- to 3.5-cm depth range from the skin surface to the chest wall. Color bar = tHb in micromoles per liter. The tHb declined from 113 μmol/L before treatment to 33 μmol/L before surgery (71% reduction). Dramatic reduction (of 55%) occurred at the end of chemotherapy cycle 3 (Fig E1 [online]). (e) MR image obtained before treatment shows 5-cm tumor. (f) MR image obtained at end of treatment shows no visible residual tumor. This patient had a complete pathologic response with no residual tumor; her tumor was Miller-Payne grade 5.

Figure 4b:

Pathologic complete response in an HER2-positive tumor. Images in 55-year-old woman with intermediate-grade IDC treated with docetaxel and carboplatin with trastuzumab acquired (a, c, e) before treatment and (b, d, f) prior to surgery. (a, b) Sonograms show ill-defined heterogeneous tumor (arrows), which was palpable at the beginning of the treatment. (c, d) Maps of tHb concentration show spatial distribution of tHb concentration reconstructed from 0.5- to 3.5-cm depth range from the skin surface to the chest wall. Color bar = tHb in micromoles per liter. The tHb declined from 113 μmol/L before treatment to 33 μmol/L before surgery (71% reduction). Dramatic reduction (of 55%) occurred at the end of chemotherapy cycle 3 (Fig E1 [online]). (e) MR image obtained before treatment shows 5-cm tumor. (f) MR image obtained at end of treatment shows no visible residual tumor. This patient had a complete pathologic response with no residual tumor; her tumor was Miller-Payne grade 5.

Figure 4c:

Pathologic complete response in an HER2-positive tumor. Images in 55-year-old woman with intermediate-grade IDC treated with docetaxel and carboplatin with trastuzumab acquired (a, c, e) before treatment and (b, d, f) prior to surgery. (a, b) Sonograms show ill-defined heterogeneous tumor (arrows), which was palpable at the beginning of the treatment. (c, d) Maps of tHb concentration show spatial distribution of tHb concentration reconstructed from 0.5- to 3.5-cm depth range from the skin surface to the chest wall. Color bar = tHb in micromoles per liter. The tHb declined from 113 μmol/L before treatment to 33 μmol/L before surgery (71% reduction). Dramatic reduction (of 55%) occurred at the end of chemotherapy cycle 3 (Fig E1 [online]). (e) MR image obtained before treatment shows 5-cm tumor. (f) MR image obtained at end of treatment shows no visible residual tumor. This patient had a complete pathologic response with no residual tumor; her tumor was Miller-Payne grade 5.

Figure 4d:

Pathologic complete response in an HER2-positive tumor. Images in 55-year-old woman with intermediate-grade IDC treated with docetaxel and carboplatin with trastuzumab acquired (a, c, e) before treatment and (b, d, f) prior to surgery. (a, b) Sonograms show ill-defined heterogeneous tumor (arrows), which was palpable at the beginning of the treatment. (c, d) Maps of tHb concentration show spatial distribution of tHb concentration reconstructed from 0.5- to 3.5-cm depth range from the skin surface to the chest wall. Color bar = tHb in micromoles per liter. The tHb declined from 113 μmol/L before treatment to 33 μmol/L before surgery (71% reduction). Dramatic reduction (of 55%) occurred at the end of chemotherapy cycle 3 (Fig E1 [online]). (e) MR image obtained before treatment shows 5-cm tumor. (f) MR image obtained at end of treatment shows no visible residual tumor. This patient had a complete pathologic response with no residual tumor; her tumor was Miller-Payne grade 5.

Figure 4e:

Pathologic complete response in an HER2-positive tumor. Images in 55-year-old woman with intermediate-grade IDC treated with docetaxel and carboplatin with trastuzumab acquired (a, c, e) before treatment and (b, d, f) prior to surgery. (a, b) Sonograms show ill-defined heterogeneous tumor (arrows), which was palpable at the beginning of the treatment. (c, d) Maps of tHb concentration show spatial distribution of tHb concentration reconstructed from 0.5- to 3.5-cm depth range from the skin surface to the chest wall. Color bar = tHb in micromoles per liter. The tHb declined from 113 μmol/L before treatment to 33 μmol/L before surgery (71% reduction). Dramatic reduction (of 55%) occurred at the end of chemotherapy cycle 3 (Fig E1 [online]). (e) MR image obtained before treatment shows 5-cm tumor. (f) MR image obtained at end of treatment shows no visible residual tumor. This patient had a complete pathologic response with no residual tumor; her tumor was Miller-Payne grade 5.

Figure 4f:

Pathologic complete response in an HER2-positive tumor. Images in 55-year-old woman with intermediate-grade IDC treated with docetaxel and carboplatin with trastuzumab acquired (a, c, e) before treatment and (b, d, f) prior to surgery. (a, b) Sonograms show ill-defined heterogeneous tumor (arrows), which was palpable at the beginning of the treatment. (c, d) Maps of tHb concentration show spatial distribution of tHb concentration reconstructed from 0.5- to 3.5-cm depth range from the skin surface to the chest wall. Color bar = tHb in micromoles per liter. The tHb declined from 113 μmol/L before treatment to 33 μmol/L before surgery (71% reduction). Dramatic reduction (of 55%) occurred at the end of chemotherapy cycle 3 (Fig E1 [online]). (e) MR image obtained before treatment shows 5-cm tumor. (f) MR image obtained at end of treatment shows no visible residual tumor. This patient had a complete pathologic response with no residual tumor; her tumor was Miller-Payne grade 5.