Long-term follow-up of breast-conserving therapy in patients with inflammatory breast cancer treated with neoadjuvant chemotherapy.

Inflammatory breast cancer (IBC) is a rare and aggressive form of breast cancer. Currently, multimodality treatment is recommended, but the optimal surgical management has not been fully elucidated. In this study, we investigated the long-term outcomes of using breast-conserving therapy in patients with IBC undergoing neoadjuvant chemotherapy (NAC). Twenty-four patients with IBC were treated from 2002 to 2006. NAC was initiated with doxorubicin and cyclophosphamide followed by paclitaxel. In addition, HER2/neu-positive patients received trastuzumab, whereas HER2/neu-negative patients received bevacizumab. Clinical response was assessed by dynamic contrast-enhanced magnetic resonance imaging before surgery and pathologic response after surgery. A partial mastectomy with sentinel lymph node biopsy and/or axillary lymph node dissection or a modified radical mastectomy was performed based on the surgeon's recommendations and patient's preference. All patients received adjuvant radiation. Of the 24 patients, seven (29%) underwent a partial mastectomy and 17 (71%) underwent a mastectomy. The overall survival rate for partial mastectomy and for mastectomy patients was 59 and 57 per cent (P = 0.49), respectively, at a median follow-up of 60 months (range, 48 to 92 months). Breast-conserving therapy can be considered in a selected group of patients who demonstrate a good response to NAC.

Next-generation sequencing reveals a Novel NSCLC ALK F1174V mutation and confirms ALK G1202R mutation confers high-level resistance to alectinib (CH5424802/RO5424802) in ALK-rearranged NSCLC patients who progressed on crizotinib.

Acquired secondary mutations in the anaplastic lymphoma kinase (ALK) gene have been identified in ALK-rearranged (ALK+) non-small-cell lung cancer (NSCLC) patients who developed disease progression while on crizotinib treatment. Here, we identified a novel secondary acquired NSCLC ALK F1174V mutation by comprehensive next-generation sequencing in one ALK+ NSCLC patient who progressed on crizotinib after a prolonged partial response to crizotinib. In a second case, we identified a secondary acquired ALK G1202R, which also confers resistance to alectinib (CH5424802/RO5424802), a second-generation ALK inhibitor that can inhibit ALK gatekeeper L1196M mutation in vitro. ALK G1202R is located at the solvent front of the ALK kinase domain and exhibits a high level of resistance to all other ALK inhibitors currently in clinical development in vitro. Comprehensive genomic profiling of resistant tumor is increasingly important in tailoring treatment decisions after disease progression on crizotinib in ALK+ NSCLC given the promise of second-generation ALK inhibitors and other therapeutic strategies.

Impact of factors affecting the residual tumor size diagnosed by MRI following neoadjuvant chemotherapy in comparison to pathology.

BACKGROUND AND OBJECTIVES: To investigate accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in breast cancer patients receiving neoadjuvant chemotherapy (NAC). METHODS: Ninety-eight patients were studied. Several MRI were performed during NAC for response monitoring, and the residual tumor size was measured on last MRI after completing NAC. Covariates, including age, tumor characteristics, biomarkers, NAC regimens, MRI scanners, and time from last MRI to operation, were analyzed. Univariate and Multivariate linear regression models were used to determine the predictive value of these covariates for MRI-pathology size discrepancy as the outcome measure. RESULTS: The mean (±SD) of the absolute difference between MRI and pathological residual tumor size was 1.0 ± 2.0 cm (range, 0-14 cm). Univariate regression analysis showed tumor type, morphology, HR status, HER2 status, and MRI scanner (1.5 T or 3.0 T) were significantly associated with MRI-pathology size discrepancy (all P < 0.05). Multivariate regression analyses demonstrated that only tumor type, tumor morphology, and biomarker status considering both HR and HER-2 were independent predictors (P = 0.0014, 0.0032, and 0.0286, respectively). CONCLUSION: The accuracy of MRI in evaluating residual tumor size depends on tumor type, morphology, and biomarker status. The information may be considered in surgical planning for NAC patients.

Baseline tumor oxygen saturation correlates with a pathologic complete response in breast cancer patients undergoing neoadjuvant chemotherapy.

Tissue hemoglobin oxygen saturation (i.e., oxygenation) is a functional imaging endpoint that can reveal variations in tissue hypoxia, which may be predictive of pathologic response in subjects undergoing neoadjuvant chemotherapy. In this study, we used diffuse optical spectroscopic imaging (DOSI) to measure concentrations of oxyhemoglobin (ctO(2)Hb), deoxy-hemoglobin (ctHHb), total Hb (ctTHb = ctO(2)Hb + ctHHb), and oxygen saturation (stO(2) = ctO(2)Hb/ctTHb) in tumor and contralateral normal tissue from 41 patients with locally advanced primary breast cancer. Measurements were acquired before the start of neoadjuvant chemotherapy. Optically derived parameters were analyzed separately and in combination with clinical biomarkers to evaluate correlations with pathologic response. Discriminant analysis was conducted to determine the ability of optical and clinical biomarkers to classify subjects into response groups. Twelve (28.6%) of 42 tumors achieved pathologic complete response (pCR) and 30 (71.4%) were non-pCR. Tumor measurements in pCR subjects had higher stO(2) levels (median 77.8%) than those in non-pCR individuals (median 72.3%, P = 0.01). There were no significant differences in baseline ctO(2)Hb, ctHHb, and ctTHb between response groups. An optimal tumor oxygenation threshold of stO(2) = 76.7% was determined for pCR versus non-pCR (sensitivity = 75.0%, specificity = 73.3%). Multivariate discriminant analysis combining estrogen receptor staining and stO(2) further improved the classification of pCR versus non-pCR (sensitivity = 100%, specificity = 85.7%). These results show that elevated baseline tumor stO(2) are correlated with a pCR. Noninvasive DOSI scans combined with histopathology subtyping may aid in stratification of individual patients with breast cancer before neoadjuvant chemotherapy.

Diagnostic performance of magnetic resonance imaging for assessing tumor response in patients with HER2-negative breast cancer receiving neoadjuvant chemotherapy is associated with molecular biomarker profile.

BACKGROUND: This study aimed to evaluate the influence of hormone receptor (HR) and Ki-67 proliferation markers in predicting the accuracy of magnetic resonance imaging (MRI) for measuring residual tumor size in patients with HER2-negative (HER2(-)) breast cancer receiving neoadjuvant chemotherapy (NAC). PATIENTS AND METHODS: Fifty-four women were studied. Patients received AC (doxorubicin (Adriamycin)/cyclophosphamide) and/or taxane-based regimens. The accuracy of MR-determined clinical complete response (CCR) was compared to pathological complete response (pCR). The size of detectable residual tumor on MRI was correlated with pathologically diagnosed tumor size using the Pearson correlation. RESULTS: MRI correctly diagnosed 16 of the 17 cases of pCR. There were 8 false-negative diagnoses: 7 HR(+) and 1 HR(-). The overall sensitivity, specificity, and accuracy of MRI were 78%, 94%, and 83%, respectively. The positive predictive value was 97% and the negative predictive value was 67%. For MRI vs. pathologically determined tumor size correlation, HR(-) cancers showed a higher correlation (R = 0.79) than did HR(+) cancers (R = 0.58). A worse MRI/pathology size discrepancy was found in HR(+) cancer than in HR(-)cancer (1.6 ± 2.8 cm vs. 0.56 ± 0.9 cm; P = .05). Tumors with low Ki-67 proliferation (< 40%) showed a larger size discrepancy than did those with high Ki-67 proliferation (≥ 40%) (1.2 ± 2.0 cm vs. 0.4 ± 0.8 cm; P = .05). CONCLUSIONS: The results showed that the diagnostic performance of MRI for patients with breast cancer undergoing NAC is associated with a molecular biomarker profile. Among HER2(-)tumors, the accuracy of MRI was worse in HR(+)cancers than in HR(-)cancers and was also worse in low-proliferation tumors than in high-proliferation tumors. These findings may help in surgical planning.

Effects of motion on optical properties in the spatial frequency domain.

Spatial frequency domain imaging (SFDI) is a noncontact and wide-field optical imaging technology currently being used to study the optical properties and chromophore concentrations of in vivo skin including skin lesions of various types. Part of the challenge of developing a clinically deployable SFDI system is related to the development of effective motion compensation strategies, which in turn, is critical for recording high fidelity optical properties. Here we present a two-part strategy for SFDI motion correction. After verifying the effectiveness of the motion correction algorithm on tissue-simulating phantoms, a set of skin-imaging data was collected in order to test the performance of the correction technique under real clinical conditions. Optical properties were obtained with and without the use of the motion correction technique. The results indicate that the algorithm presented here can be used to render optical properties in moving skin surfaces with fidelities within 1.5% of an ideal stationary case and with up to 92.63% less variance. Systematic characterization of the impact of motion variables on clinical SFDI measurements reveals that until SFDI instrumentation is developed to the point of instantaneous imaging, motion compensation is necessary for the accurate localization and quantification of heterogeneities in a clinical setting.

Comparison of breast density measured on MR images acquired using fat-suppressed versus nonfat-suppressed sequences.

PURPOSE: To investigate the difference of MR percent breast density measured from fat-suppressed versus nonfat-suppressed imaging sequences. METHODS: Breast magnetic resonance imaging (MRI) with and without fat suppression was acquired from 38 subjects. Breasts were divided into subgroups of different morphological patterns ("central" and "intermingled" types). Breast volume, fibroglandular tissue volume, and percent density were measured. The results were compared using nonparametric statistical tests and regarded as significant at p < 0.05. RESULTS: Breast volume, fibroglandular volume, and percent density between fat-suppressed and nonfat-suppressed sequences were highly correlated. Breast volumes measured on these two sequences were almost identical. Fibroglandular tissue volume and percent density, however, had small (<5%) yet significant differences between the two sequences-they were both higher on the fat-suppressed sequence. Intraobserver variability was within 4% for both sequences and different morphological types. The fibroglandular tissue volume measured on downsampled images showed a small (<5%) yet significant difference. CONCLUSIONS: The measurement of breast density made on MRI acquired using fat-suppressed and nonfat-suppressed T1W images was about 5% difference, only slightly higher than the intraobserver variability of 3%-4%. When the density data from multiple centers were to be combined, evaluating the degree of difference is needed to take this difference into account.

Diffuse optical spectroscopic imaging correlates with final pathological response in breast cancer neoadjuvant chemotherapy.

Diffuse optical spectroscopic imaging (DOSI) non-invasively and quantitatively measures tissue haemoglobin, water and lipid. Pilot studies in small groups of patients demonstrate that DOSI may be useful for longitudinal monitoring and predicting breast cancer neoadjuvant chemotherapy pathological response. This study evaluates the performance of a bedside DOSI platform in 34 breast cancer patients followed for several months. DOSI optical endpoints obtained at multiple timepoints are compared with final pathological response. Thirty-six stage II/III breast cancers (34 patients) were measured in vivo with DOSI prior to, in the middle of and after the completion of pre-surgical neoadjuvant chemotherapy. Cancer therapies ranged from standard anthracyclines to targeted therapies. Changes in DOSI-measured parameters at each timepoint were compared against final surgical pathology. Absolute changes in the tumour-to-normal (T/N) ratio of tissue deoxyhaemoglobin concentration (ctHHb) and relative changes in the T/N ratio of a tissue optical index (TOI) were most sensitive and correlate to pathological response. Changes in ctHHb and TOI were significantly different between tumours that achieved pathological complete response (pCR) versus non-pCR. By therapy midpoint, mean TOI-T/N changes were 47±8 versus 20±5 per cent for pCR versus non-pCR subjects, respectively (Z=0.011). Changes in ctHHb and TOI scaled significantly with the degree of pathological response (non-, partial and complete). DOSI measurements of TOI separated pCR from non-pCR by therapy midpoint regardless of drug or dosing strategy. This approach is well suited to monitoring breast tumour response and may provide feedback for optimizing therapeutic outcomes and minimizing side-effects.

Breast cancer: evaluation of response to neoadjuvant chemotherapy with 3.0-T MR imaging.

PURPOSE: To assess how the molecular biomarker status of a breast cancer, including human epidermal growth factor receptor 2 (HER2), hormone receptors, and the proliferation marker Ki-67 status, affects the diagnosis at 3.0-T magnetic resonance (MR) imaging. MATERIALS AND METHODS: This study was approved by the institutional review board and was HIPAA compliant. Fifty patients (age range, 28-82 years; mean age, 49 years) receiving neoadjuvant chemotherapy were monitored with 3.0-T MR imaging. The longest dimension of the residual cancer was measured at MR imaging and correlated with pathologic findings. Patients were further divided into subgroups on the basis of HER2, hormone receptor, and Ki-67 status. Pathologic complete response (pCR) was defined as when there were no residual invasive cancer cells. The Pearson correlation was used to correlate MR imaging-determined and pathologic tumor size, and the unpaired t test was used to compare MR imaging-pathologic size discrepancies. RESULTS: Of the 50 women, 14 achieved pCR. There were seven false-negative diagnoses at MR imaging. The overall sensitivity, specificity, and accuracy for diagnosing invasive residual disease at MR imaging were 81%, 93%, and 84%, respectively. The mean MR imaging-pathologic size discrepancy was 0.5 cm ± 0.9 (standard deviation) for HER2-positive cancer and 2.3 cm ± 3.5 for HER2-negative cancer (P = .009). In the HER2-negative group, the size discrepancy was smaller for hormone receptor-negative than for hormone receptor-positive cancers (1.0 cm ± 1.1 vs 3.0 cm ± 4.0, P = .04). The size discrepancy was smaller in patients with 40% or greater Ki-67 expression (0.8 cm ± 1.1) than in patients with 10% or less Ki-67 expression (3.9 cm ± 5.1, P = .06). CONCLUSION: The diagnostic accuracy of breast MR imaging is better in more aggressive than in less aggressive cancers. When MR imaging is used for surgical planning, caution should be taken with HER2-negative hormone receptor-positive cancers.

Optical imaging of breast cancer oxyhemoglobin flare correlates with neoadjuvant chemotherapy response one day after starting treatment.

Approximately 8-20% of breast cancer patients receiving neoadjuvant chemotherapy fail to achieve a measurable response and endure toxic side effects without benefit. Most clinical and imaging measures of response are obtained several weeks after the start of therapy. Here, we report that functional hemodynamic and metabolic information acquired using a noninvasive optical imaging method on the first day after neoadjuvant chemotherapy treatment can discriminate nonresponding from responding patients. Diffuse optical spectroscopic imaging was used to measure absolute concentrations of oxyhemoglobin, deoxyhemoglobin, water, and lipid in tumor and normal breast tissue of 24 tumors in 23 patients with untreated primary breast cancer. Measurements were made before chemotherapy, on day 1 after the first infusion, and frequently during the first week of therapy. Various multidrug, multicycle regimens were used to treat patients. Diffuse optical spectroscopic imaging measurements were compared with final postsurgical pathologic response. A statistically significant increase, or flare, in oxyhemoglobin was observed in partial responding (n = 11) and pathologic complete responding tumors (n = 8) on day 1, whereas nonresponders (n = 5) showed no flare and a subsequent decrease in oxyhemoglobin on day 1. Oxyhemoglobin flare on day 1 was adequate to discriminate nonresponding tumors from responding tumors. Very early measures of chemotherapy response are clinically convenient and offer the potential to alter treatment strategies, resulting in improved patient outcomes.

Frequent optical imaging during breast cancer neoadjuvant chemotherapy reveals dynamic tumor physiology in an individual patient.

RATIONALE AND OBJECTIVES: Imaging tumor response to neoadjuvant chemotherapy in vivo offers unique opportunities for patient care and clinical decision-making. Detailed imaging studies may allow oncologists to optimize therapeutic drug type and dose based on individual patient response. Most radiologic methods are used sparingly because of cost; thus, important functional information about tumor response dynamics may be missed. In addition, current clinical standards are based on determining tumor size changes; thus, standard anatomic imaging may be insensitive to early or frequent biochemical responses. Because optical methods provide functional imaging end points, our objective is to develop a low-barrier-to-access bedside approach that can be used for frequent, functional assessment of dynamic tumor physiology in individual patients. MATERIALS AND METHODS: Diffuse Optical Spectroscopic Imaging (DOSI) is a noninvasive, bedside functional imaging technique that quantifies the concentration and molecular state of tissue hemoglobin, water, and lipid. Pilot clinical studies have shown that DOSI may be a useful tool for quantifying neoadjuvant chemotherapy response, typically by comparing the degree of change in tumor water and deoxy-hemoglobin concentration before and after therapy. Patient responses at 1 week and mid-therapy have been used to predict clinical outcome. In this report, we assess the potential value of frequent DOSI monitoring by performing measurements on 19 different days in a 51-year-old subject with infiltrating ductal carcinoma (initial tumor size 60 x 27 mm) who received neoadjuvant chemotherapy (anthracyclines and bevacizumab) over an 18-week period. RESULTS: A composite index, the Tissue Optical Index (TOI), showed a significant ( approximately 50%) decrease over the nearly 18 weeks of chemotherapy. Tumor response was sensitive to the type of chemotherapy agent, and functional indices fluctuated in a manner consistent with dynamic tumor physiology. Final pathology revealed 4 mm of residual disease, which was detectible by DOSI at the conclusion of chemotherapy before surgery. CONCLUSION: This case study suggests that DOSI may be a bedside-capable tool for frequent longitudinal monitoring of therapeutic functional response to neoadjuvant chemotherapy.

Characterization of metabolic differences between benign and malignant tumors: high-spectral-resolution diffuse optical spectroscopy.

PURPOSE: To develop a near-infrared spectroscopic method to identify breast cancer biomarkers and to retrospectively determine if benign and malignant breast lesions could be distinguished by using this method. MATERIALS AND METHODS: The study was HIPAA compliant and was approved by the university institutional review board. Written informed consent was obtained. By using self-referencing differential spectroscopy (SRDS) analysis, the existence of specific spectroscopic signatures of breast lesions on images acquired by using diffuse optical spectroscopy imaging in the wavelength range (650-1000 nm) was established. The SRDS method was tested in 60 subjects (mean age, 38 years; age range, 22-74 years). There were 17 patients with benign breast tumors and 22 patients with malignant breast tumors. There were 21 control subjects. RESULTS: Discrimination analysis helped separate malignant from benign tumors. A total of 40 lesions (22 malignant and 18 benign) were analyzed. Twenty were true-positive lesions, 17 were true-negative lesions, one was a false-positive lesion, and two were false-negative lesions (sensitivity, 91% [20 of 22]; specificity, 94% [17 of 18]; positive predictive value, 95% [20 of 21]; and negative predictive value, 89% [17 of 19]). CONCLUSION: The SRDS method revealed localized tumor biomarkers specific to pathologic state.

Effect of contact force on breast tissue optical property measurements using a broadband diffuse optical spectroscopy handheld probe.

We investigated the effects of operator-applied force on diffuse optical spectroscopy (DOS) by integrating a force transducer into the handheld probe. Over the typical range of contact forces measured in the breasts of eight patients, absorption and reduced scattering coefficients (650 to 1000 nm) variance was 3.1 +/- 1.0% and 1.0 +/- 0.4%. For trained operators, we observed <5% variation in hemoglobin and <2% variation in water and lipids. Contact force is not a significant source of variation, most likely because of a relatively wide probe surface area and the stability of the DOS method for calculating tissue optical properties.

Diffuse optical spectroscopy measurements of healing in breast tissue after core biopsy: case study.

Diffuse optical spectroscopy (DOS) has been used to monitor and predict the effects of neoadjuvant (i.e., presurgical) chemotherapy in breast cancer patients in several pilot studies. Because patients with suspected breast cancers undergo biopsy prior to treatment, it is important to understand how biopsy trauma influences DOS measurements in the breast. The goal of this study was to measure the effects of a standard core breast biopsy on DOS measurements of tissue deoxyhemoglobin, hemoglobin, water, and bulk lipid concentrations. We serially monitored postbiopsy effects in the breast tissue in a single subject (31-year-old premenopausal female) with a 37x18x20 mm fibroadenoma. A baseline measurement and eight weekly postbiopsy measurements were taken with a handheld DOS imaging instrument. Our instrument used frequency domain photon migration combined with broadband steady-state spectroscopy to characterize tissues via quantitative measurements of tissue absorption and reduced scattering coefficients from 650 to 1000 nm. The concentrations of significant near-infrared (NIR) absorbers were mapped within a 50 cm(2) area over the biopsied region. A 2-D image of a contrast function called the tissue optical index (TOI=deoxyhemoglobinxwaterbulk lipid) was generated and revealed that a minimum of 14 days postbiopsy was required to return TOI levels in the biopsied area to their prebiopsy levels. Changes in the TOI images of the fibroadenoma also reflected the progression of the patient's menstrual cycle. DOS could therefore be useful in evaluating both wound-healing response and the effects of hormone and hormonal therapies in vivo.

Impact of MRI-evaluated neoadjuvant chemotherapy response on change of surgical recommendation in breast cancer.

OBJECTIVE: To investigate how MRI imaging of neoadjuvant chemotherapy (NAC) tumor response affects the recommendation for optimal breast cancer surgery, both before and after NAC. SUMMARY BACKGROUND DATA: Understanding how imaging findings are incorporated into surgeons' decision-making processes will help establish appropriate imaging guidelines for recommending breast conservation surgery (BCS) after the NAC. METHODS: Seventy-six breast cancer patients undergoing NAC with MRI follow-up studies were analyzed. Two experienced breast surgeons reviewed all cases. An initial surgical recommendation was made based on the pre-NAC lesion presentation; a subsequent surgical recommendation was made based on the post-NAC tumor response. Finally, the pathology results were disclosed and the surgeons were asked to decide on the optimal definitive surgical procedure. MRI findings throughout the entire course of the NAC were analyzed to understand how they affected different recommendations. RESULTS: Before the NAC, a large tumor size or extent of disease were the primary determinant factors for mastectomy. In this study, the mean tumor size was 5.3 +/- 3.4 cm (RECIST) in the mastectomy group and 3.2 +/- 1.6 cm in the lumpectomy group (P = 0.0001). After the NAC, based on consensus recommendations, 21 mastectomy candidates remained for mastectomy, with tumor size decreasing from 7.4 +/- 4.5 to 1.5 +/- 2.5 cm, and 22 mastectomy candidates were changed to lumpectomy, with tumor size decreasing from 4.2 +/- 2.1 to 0.4 +/- 0.6 cm. When the final pathology revealed pCR or minimal residual disease, the surgeons agreed that BCS is the optimal procedure. On the other hand, for a large extent of residual disease, mastectomy should be performed. CONCLUSION: In patients who had more extensive pretreatment disease, despite an excellent response to NAC, the surgeons still tended to apply an aggressive approach and recommended mastectomy. Given that the confirmation of pCR or minimal residual disease would change surgeons' recommendations for less aggressive, conservation surgery, the maturity of MRI for NAC response prediction may provide reliable staging information to aid in the recommendation of the optimal surgical procedure.

Regional differences in the use of sentinel lymph node biopsy for melanoma: a potential quality measure.

Sentinel lymph node biopsy (SLNB) provides accurate nodal staging in patients with melanoma. However, its prevalence across geographic regions is unknown. Our aim was to determine if SLNB for melanoma has been widely adopted throughout the United States. All patients in the Surveillance, Epidemiology and End Results (SEER) cancer registry for 2004 with melanoma were evaluated. Data were collected for demographics, depth of melanoma, and type of nodal evaluation (regional lymph node dissection vs SLNB). Registry sites were categorized into West, Midwest, Northeast, and Southeast. Chi2 analysis was performed to identify regional differences in receipt of SLNB. Overall, the West region (n = 2352) had a higher use of SLNB compared with the Midwest (n = 497), Northeast (n = 630), and Southeast (n = 268) regions (82.1% vs 77.9%, 65.4%, and 60.1%, respectively; P < 0.001). Intermediate-thickness (1 to 4 mm) melanomas had differences in SLNB use between the West and Midwest (83.6% and 81.4%) versus the Northeast and Southeast (66.3% and 60.2%) (P < 0.05). This population-based analysis shows low use of SLNB for melanoma in some U.S. regions. Further studies need to address the reasons for these differences and target ways to improve rates. Results suggest that SLNB may be considered as a potential quality measure.

The predictive value of sentinel lymph node biopsy in locally advanced breast cancer patients who have undergone neoadjuvant chemotherapy.

With the increasing usage of neoadjuvant chemotherapy (NAC) in locally advanced breast cancer (LABC), there is the need to investigate the routine axillary node dissections performed in this group of patients. Controversy exists about the utility of sentinel node biopsy (SNB), either before or after NAC. With the addition of trastuzumab in the treatment of Her2/neu-positive LABC patients, the validity of SNB in this subset population needs to be investigated. A retrospective study of 20 patients who underwent NAC for LABC was undertaken. The pathology of the axillary nodes, sentinel nodes, and primary tumor after neoadjuvant chemotherapy were examined. Twenty patients underwent NAC with doxorubicin and cyclophosphamide, followed sequentially by paclitaxel and carboplatin, with or without trastuzumab based on Her2/neu status. Post chemotherapy, 20 patients underwent mastectomy or lumpectomy with SNB with axillary node dissections. The overall accuracy of SNB was 95 per cent with a false-negative rate of 14 per cent (1/7). In Her2/neu-positive patients, overall accuracy was 100 per cent (8/8) and a false-negative rate of zero per cent. Sentinel node biopsy is a viable option in patients who have undergone NAC. Her2/neu-positive patients who had undergone NAC with trastuzumab had comparable accuracy for sentinel node biopsy in predicting axillary node status.

Do breast columnar cell lesions with atypia need to be excised?

Columnar cell lesion with atypia (CCLA) is a newly recognized pathologic entity seen in breast specimens. The breast cancer risk associated with this finding is unclear, although CCLA had been found adjacent to both in situ and invasive carcinomas, but the incidence is unknown. Breast specimens from patients with a columnar cell lesion were reviewed by a pathologist for atypia. Twenty-one specimens with CCLA were identified [core biopsy (8), excisional biopsy (11), and simple mastectomy (2)]. Six of eight specimens with CCLA on core had adjacent abnormal pathology: infiltrating ductal carcinoma (IDC)/lobular carcinoma in situ (LCIS) (1), ductal carcinoma in situ (DCIS)/LCIS (1), DCIS (1), LCIS (1), and papillomatosis (2). Five of 11 specimens with CCLA on excisional biopsy had adjacent abnormal pathology: IDC (3), DCIS/LCIS (1), and atypical ductal hyperplasia/papilloma (1). Two of two simple mastectomy specimens had CCLA associated with IDC (1) and DCIS (1). Overall, abnormal pathology was found adjacent to CCLA in 62 per cent of specimens (13/21). Breast pathologic specimens containing a columnar cell lesion should be carefully examined for atypia. Surgical excision is warranted for CCLA found on core biopsy. The future risk of breast cancer based on the finding of CCLA alone requires further investigation.