Impact of Chemotherapy-Induced Ovarian Dysfunction on Response to Neoadjuvant Chemotherapy in Breast Cancer.

BACKGROUND: The association between chemotherapy-induced ovarian dysfunction (CIOD) and response to neoadjuvant chemotherapy (NAC) is not known. We therefore investigated the impact of CIOD on response to NAC in breast cancer patients according to estrogen receptor (ER) status. METHODS: In total, 343 premenopausal breast cancer patients treated with NAC between 2006 and 2010 were analyzed. Clinical responses were determined based on changes in tumor size measured using breast MRI. Patients with complete response or partial response were considered to have clinical response. RESULTS: After completion of NAC, 264 of 343 patients (76.9 %) developed CIOD. The clinical response rate was significantly higher in patients with CIOD than those without CIOD (65.2 vs. 51.9 %; p = 0.033). Additionally, the mean follicle-stimulating hormone (FSH) level after NAC was significantly higher in patients with clinical response (FSH 68.7 ± 34.5 vs. 59.8 ± 34.3 IU/L; p = 0.021). Multivariate analysis showed an independent association of CIOD to clinical response (OR 0.523, 95 % CI 0.297-0.918; p = 0.024). However, we observed no differences in the pathologic complete response (pCR) rate between patients with and without CIOD (8.7 vs. 6.3 %; p = 0.497). Subgroup analysis according to ER status showed that the association between CIOD and clinical response was significant in ER-positive but not ER-negative breast cancer (p = 0.025 and 0.818, respectively). CONCLUSIONS: CIOD during NAC is significantly associated with clinical response, but not pCR. Moreover, this association is only observed in ER-positive breast cancer, suggesting that the moderate difference in response to NAC is possibly a hormonal effect of chemotherapy-induced ovarian dysfunction.

Survival Improvement in Korean Breast Cancer Patients Due to Increases in Early-Stage Cancers and Hormone Receptor Positive/HER2 Negative Subtypes: A Nationwide Registry-Based Study.

PURPOSE: The aim of this study was to investigate whether the observed changes over time in the survival rates vary according to the intrinsic subtypes of breast cancer diagnosed. METHODS: Data from 46,320 breast cancer patients in the Korean Breast Cancer Registry who underwent surgery between 1999 and 2006 were reviewed. Among them, results from 25,887 patients with available data about the status of estrogen receptor, progesterone receptor, and human epidermal growth factor receptor 2 (HER2) were analyzed. Patients were classified into two cohorts according to the year in which they underwent surgery: 1999-2002 and 2003-2006. RESULTS: The patients treated in the latter time period showed significantly better overall survival (OS) compared with those in the former period when adjusted for follow-up duration. The proportion of hormone receptor+/HER2-subtype and stage I breast cancer were significantly higher in the latter period (47.4% vs. 54.6%, p<0.001; 31.0% vs. 39.6%, p<0.001, respectively). Improvement in OS between the former and latter periods was seen in all subtypes of breast cancer, including triple-negative cancers (all p-values <0.001 in univariate and multivariate analyses). CONCLUSION: Improvement in survival in Korean breast cancer patients over the study years is being observed in all subtypes of breast cancer, implying that increases in both early-stage detection and the proportion of less aggressive cancers contribute to this improvement.

Low rates of additional cancer detection by magnetic resonance imaging in newly diagnosed breast cancer patients who undergo preoperative mammography and ultrasonography.

PURPOSE: We evaluated the efficacy of breast magnetic resonance imaging (MRI) for detecting additional malignancies in breast cancer patients newly diagnosed by breast ultrasonography and mammography. METHODS: We retrospectively reviewed the records of 1,038 breast cancer patients who underwent preoperative mammography, bilateral breast ultrasonography, and subsequent breast MRI between August 2007 and December 2010 at single institution in Korea. MRI-detected additional lesions were defined as those lesions detected by breast MRI that were previously undetected by mammography and ultrasonography and which would otherwise have not been identified. RESULTS: Among the 1,038 cases, 228 additional lesions (22.0%) and 30 additional malignancies (2.9%) were detected by breast MRI. Of these 228 lesions, 109 were suspected to be malignant (Breast Imaging-Reporting and Data System category 4 or 5) on breast MRI and second-look ultrasonography and 30 were pathologically confirmed to be malignant (13.2%). Of these 30 lesions, 21 were ipsilateral to the main lesion and nine were contralateral. Fourteen lesions were in situ carcinomas and 16 were invasive carcinomas. The positive predictive value of breast MRI was 27.5% (30/109). No clinicopathological factors were significantly associated with additional malignant foci. CONCLUSION: Breast MRI was useful in detecting additional malignancy in a small number of patients who underwent ultrasonography and mammography.

Preoperative serum tissue polypeptide-specific antigen is a valuable prognostic marker in breast cancer.

Tissue polypeptide-specific antigen (TPS), a specific epitope structure of a peptide in serum associated with human cytokeratin 18, is linked to the proliferative activity of tumors. Here, we aimed to identify the association between the preoperative serum TPS level and outcome in breast cancer patients. We assayed preoperative serum TPS levels in 1,477 breast cancer patients treated between June 2000 and December 2006. The TPS level was measured with a one-step solid phase radiometric sandwich assay detecting the M3 epitope on cytokeratin 18 fragments. The cutoff value was 80 U/L. Among the 1,477 breast cancer patients examined, preoperative serum TPS level was elevated (>80 U/L) in 290 patients (19.6%). Age (>45 years), tumor size (>2 cm), nodal metastasis, negative progesterone receptor and human epidermal growth factor receptor 2 were associated with elevated TPS. Evidence of recurrence was observed in 229 patients (15.6%). Elevated TPS was associated with poor disease-free survival (p < 0.001) and overall survival (p < 0.001). In a multivariate analysis using the Cox proportional regression model, elevated TPS was an independent prognostic factor for disease-free survival (p = 0.001) and overall survival (p = 0.026). Furthermore, in subgroup analysis based on molecular subtype, the prognostic effect of preoperative TPS on survival (OS: HR 2.614, p = 0.003; DFS: HR 1.895, p = 0.001) was identified only in the luminal A subtype. Elevated preoperative serum TPS level is associated with poor breast cancer outcomes. Based on these findings, we conclude that preoperative TPS is a valuable biomarker for clinical use in predicting outcomes in breast cancer patients.

Breast density change as a predictive surrogate for response to adjuvant endocrine therapy in hormone receptor positive breast cancer.

INTRODUCTION: Anti-estrogen therapy has been shown to reduce mammographic breast density (MD). We hypothesized that a short-term change in breast density may be a surrogate biomarker predicting response to adjuvant endocrine therapy (ET) in breast cancer. METHODS: We analyzed data for 1,065 estrogen receptor (ER)-positive breast cancer patients who underwent surgery between 2003 and 2006 and received at least 2 years of ET, including tamoxifen and aromatase inhibitors. MD was measured using Cumulus software 4.0 and expressed as a percentage. MD reduction (MDR) was defined as the absolute difference in MD of mammograms taken preoperatively and 8-20 months after the start of ET. RESULTS: At a median follow-up of 68.8 months, the overall breast cancer recurrence rate was 7.5% (80/1065). Mean MDR was 5.9% (range, -17.2% to 36.9%). Logistic regression analysis showed that age < 50 years, high preoperative MD, and long interval between start of ET to follow-up mammogram were significantly associated with larger MDR (p < 0.05). In a survival analysis, tumor size, lymph node positivity, high Ki-67 (≥ 10%), and low MDR were independent factors significantly associated with recurrence-free survival (p < 0.05). Compared with the group showing the greatest MDR (≥ 10%), the hazard ratios for MDRs of 5-10%, 0-5%, and < 0% were 1.33, 1.92, and 2.26, respectively. CONCLUSIONS: MD change during short-term use of adjuvant ET was a significant predictor of long-term recurrence in women with ER-positive breast cancer. Effective treatment strategies are urgently needed in patients with low MDR despite about 1 year of ET.

Factors associated with upstaging from ductal carcinoma in situ following core needle biopsy to invasive cancer in subsequent surgical excision.

OBJECTIVES: The present study tried to identify factors predictive of upstaging from ultrasound-guided core needle biopsy (CNB)-diagnosed ductal carcinoma in situ (DCIS) to invasive cancer after surgical excision. MATERIALS AND METHODS: We enrolled 506 female CNB-diagnosed DCIS patients who underwent subsequent surgical excision between January 2000 and February 2011. A retrospective analysis of patients undergone core needle biopsy and subsequent surgical excision was performed. Ultrasonography guided CNB was performed using either an 8-, 11-gauge vacuum-assisted method, or a 14-gauge needle automated gun method. RESULTS: The overall upstaging rate was 42.7% (216/506). Multivariate analysis found that a palpable lesion, a lesion size >20 mm, a high grade lesion, and use of the 14-gauge needle method were independently associated with upstaging (p < 0.05 for all variables). We designed a scoring system to predict lymph node positivity in these patients, and the subsequent ROC curve showed an AUC value of 0.746 (p < 0.001, 95% CI: 0.66-0.82). Patient with a non-high grade lesion that was ≤20 mm in size carried no risk of lymph node positivity. CONCLUSION: Upstaging was associated with lesions that were large, palpable or high grade. It was also associated with use of the 14-gauge needle method. Our scoring system might be helpful to identify patients who do not require sentinel lymph node biopsy.

Limited value and utility of breast MRI in patients undergoing breast-conserving cancer surgery.

BACKGROUND: Our aim was to compare the accuracy of magnetic resonance imaging (MRI) and ultrasonography (US) in measuring the size of invasive breast cancer (IBC) and carcinoma in situ (CIS). We also examined the utility of routinely performing MRI in addition to US before breast-conserving surgery (BCS). PATIENTS AND METHODS: Data from 1558 consecutive patients diagnosed with IBC and/or CIS between 2003 and 2005 were reviewed. For comparing the accuracy of US and MRI, paired t test was done comparing pathologic and imaging (US and MRI) tumor size in 821 patients who received both breast US and MRI. In instance of attempted BCS (n = 794), operative approach, resection margins, and clinical outcomes of non-MRI and MRI groups were compared. RESULTS: For CIS, IBC without CIS, and IBC with CIS, MRI was more accurate in estimating tumor size than US. When BCS was attempted (n = 794), the rate of tumor involvement in initial resection margins did not differ between non-MRI and MRI groups (23.0% and 23.4%, P = .926). Similarly, rates of re-excision (13.1% vs 17.5%, P = .130) and conversion to mastectomy (2.3% vs 2.1%, P = .893) were comparable, as were ipsilateral breast tumor recurrence, locoregional recurrence, and disease-free survival (log rank P = .284, .950, and .955, respectively). CONCLUSIONS: Breast MRI provided more accurate estimates of tumor size, correlating better with pathologic tumor size than US for both IBC and CIS. However, no clear benefit in terms of lower re-excision rate, higher breast conservation success, or reduced recurrence emerged for routine use of breast MRI before BCS.

Validation of a scoring system for predicting malignancy in patients diagnosed with atypical ductal hyperplasia using an ultrasound-guided core needle biopsy.

PURPOSE: The need for surgical excision in patients with ultrasound-guided core needle biopsy (CNB)-diagnosed atypical ductal hyperplasia (ADH) remains an issue of debate. The present study sought to validate a scoring system (the U score, for underestimation) that we have previously developed for predicting malignancy in CNB-diagnosed ADH. METHODS: The study prospectively enrolled 85 female patients with CNB-diagnosed ADH who underwent subsequent surgical excision. Underestimation was defined as a surgical specimen having malignant foci. RESULTS: The overall underestimation rate was 37% (31/85). Multivariate analysis showed that a clinically palpable mass, microcalcification on imaging, size >15 mm and a patient age of ≥50 years were independently associated with underestimation. When applied to the scoring system, the validation score was significant (p<0.001; area under the curve, 0.852). No patient with a U score <3.5 had an underestimated lesion. CONCLUSION: The present study successfully validated the efficacy of our scoring system for predicting malignancy in CNB-diagnosed ADH. A U score of ≤3.5 indicates that surgical excision may not be necessary.