Consecutive Invasive Breast Cancer Patients Research Articles

Diagnostic Accuracy of Axillary Ultrasound for Prediction of Axillary Pathologic Response after Neoadjuvant Treatment in Breast Cancer.

Background: In the era of NAT, to accurately predict pathologic response is a great challenge, which might influence surgical approach for breast and axilla. Axillary staging via imaging methods as an adjunct have long been used with various reported accuracy rates. However, the role of preoperative axillary ultrasonography (AUS) in clinical N0 patients after NAT is still controversial. The primary goal of the present study was to evaluate the precision of preoperative AUS for identifying pathologic complete response (ypCR = ypT0, ypN0) after NAT. Methods: A single-institution, retrospective review of a prospectively maintained database was analyzed to identify breast cancer patients treated with NAT. Only those patients who underwent AUS and 18F-FDG-PET/CT before and after NAT with documentation of clinical and radiological response were incorporated for outcome analysis. Results: In 253 consecutive invasive breast cancer patients axillary ypN0 disease was achieved in 67.19%. In 11.23% ynon-pCR patients AUS failed to detect residual disease presence 80% of which were ITCs and micrometastases. Macrometastasis was present in 21.73% (55/253) of the cases 98.18% (54/55) of which was determined by AUS. Overall accuracy for axillary pCR was found to be 89.32% for AUS and 76.28 % for 18-FDG-PET/CT. The false negative rate (FNR) of AUS and 18-FDG-PET/CT was 12.04% and 15.59%, respectively. The PPV of AUS was higher in Luminal-like tumors (%87.69), whereas HER-2 positive (%100) and triple-negative (93.47%) subtypes had higher NPV. Conclusions: AUS is a beneficial tool with the potential of accurate prediction of pCR in more than 80% of patients following NAT. Nevertheless, in cases of residual ITCs and micrometastasis the accuracy of US should be interrogated cautiously.

Searching for a link between Ki-67 values and HER2 absence in 297 patients with triple-negative breast cancer.

e12551 Background: Based on the report that in ER- invasive breast cancer (IBC) patients, the absence of HER2 might be linked to their Ki-67 values ( Kurbel et al. BMC Cancer 2017;17:231), this relation was searched in 297 consecutive IBC patients with triple negative tumors, treated at two Croatian hospitals. Methods: All 297 patients had ER and PgR negative IBC, The HER2 expression was IHC absent in 211 pts.; IHC 1+ in 62 pts.: IHC 2+ & ISH negative in 24 pts. Based on the cited reference that the Expectation maximization clustering (EM) of the pooled IBC Ki-67 values detects three clusters, regardless of the tumor type, the same approach was used. Differences in the distribution of HER2 values were tested by the χ2 test. Results: Three EM clusters were detected among the pooled Ki67 values: LMA (low mitotic activity) cluster: 109 cases with Ki-67 < 44%; IMA (intermediate mitotic activity) cluster: 96 cases, Ki-67 from 44 to 70% and HMA (high mitotic activity) cluster: 92 cases, Ki-67 > 70%. Beside the Ki-67, distribution of HER2 values was dependent on the age (Chi-square: 25.0309, df = 12, p = 0.014677), as shown here: In patients younger than 46, the HMA cluster was 32% larger than expected. Out of 29 HMA pts, 24 had HER2 absent tumors (53% more than expected). In patients aged 46 to 55, the IMA cluster was 27% larger than expected and out of 30 IMA, 24 had HER2 absent tumors (43% more than expected). In patients older than 55, the LMA cluster was 21% larger than expected, due to more patients with tumors positive for HER2. Out of 68 LMA pts., 22 pts. had tumors with HER2 expression (1+/2+), 40% more than expected. Conclusions: HER2 absent triple negative IBCs might be biologically different from the triple negative and HER2 1+/2+ tumors. The former were linked to pts younger than 55 and Ki-67 values > 43%. The latter showed opposite affinities, age above 55 and Ki-67 < 44%. Based on this, the absence of HER2 in triple negative IBC seems a valid target for future research.[Table: see text]

Association Between Imaging Characteristics and Different Molecular Subtypes of Breast Cancer

Breast cancer can be divided into four major molecular subtypes based on the expression of hormone receptor (estrogen receptor and progesterone receptor), human epidermal growth factor receptor 2, HER2 status, and molecular proliferation rate (Ki67). In this study, we sought to investigate the association between breast cancer subtype and radiological findings in the Chinese population. Medical records of 300 consecutive invasive breast cancer patients were reviewed from the database: the Breast Imaging Reporting and Data System. The imaging characteristics of the lesions were evaluated. The molecular subtypes of breast cancer were classified into four types: luminal A, luminal B, HER2 overexpressed (HER2), and basal-like breast cancer (BLBC). Univariate and multivariate logistic regression analyses were performed to assess the association between the subtype (dependent variable) and mammography or 15 magnetic resonance imaging (MRI) indicators (independent variables). Luminal A and B subtypes were commonly associated with "clustered calcification distribution," "nipple invasion," or "skin invasion" (P <0.05). The BLBC subtype was more commonly associated with "rim enhancement" and persistent inflow type enhancement in delayed phase (P <0.05). HER2 overexpressed cancers showed association with persistent enhancement in the delayed phase on MRI and "clustered calcification distribution" on mammography (P <0.05). Certain radiological features are strongly associated with the molecular subtype and hormone receptor status of breast tumor, which are potentially useful tools in the diagnosis and subtyping of breast cancer.

The role of ultrasonographic findings to predict molecular subtype, histologic grade, and hormone receptor status of breast cancer.

The correlation between imaging findings and pathologic characteristics of tumors may provide information for diagnosis and treatment of cancer. The aim of this study is to determine whether ultrasound features of breast cancer are associated with molecular subtype, histologic grade, and hormone receptor status, as well as assess the predictive value of these features. A total of 201 consecutive invasive breast cancer patients were reviewed from the database according to the Breast Imaging and Reporting Data System (BI-RADS). Tumor margins were classified as circumscribed and noncircumscribed. Noncircumscribed group was divided into indistinct, spiculated, angular, and microlobulated. The posterior acoustic features were divided into four categories: shadowing, enhancement, no change, and mixed pattern. Tumors with posterior shadowing were more likely to be of nontriple negative subtype (odds ratio [OR], 7.42; 95% CI, 2.10-24.99; P = 0.002), low histologic grade (grade 1 or 2 vs. grade 3: OR, 2.42; 95% CI, 1.34-4.35; P = 0.003) and having at least one positive receptor (OR, 3.36; 95% CI, 1.55-7.26; P = 0.002). Tumors with circumscribed margins were more often triple-negative subtype (OR, 6.72; 95% CI, 2.56-17.65; P < 0.001), high grade (grade 3 vs. grade 1 or 2: OR, 5.42; 95% CI, 2.66-11.00; P < 0.001) and hormone receptor negative (OR, 4.87; 95% CI, 2.37-9.99; P < 0.001). Sonographic features are strongly associated with molecular subtype, histologic grade, and hormone receptor status of the tumor. These findings may separate triple-negative breast cancer from other molecular subtypes.

Pathological features and clinical outcomes of breast cancer according to levels of oestrogen receptor expression

Historically, nuclear staining of ≥10% of invasive tumour cells has been used for oestrogen receptor (ER) positivity. In 2010, ASCO/CAP guidelines recommended the cut-off value be changed to nuclear staining of ≥1%. This study will analyse the relationships between levels of ER expression and clinicopathological features and clinical outcomes, with an emphasis on the ER 1-10% subgroup. We analysed clinicopathological features in five subgroups based on ER expression levels in 1700 consecutive invasive breast cancer patients diagnosed and treated at our institution between 2000 and 2011. Of the cases, 24% had ER expression <1%, 2% were ER 1-10%, 5% were 11-50%, 5% were 51-70% and 64% were 71-100%. We observed four subgroups of patient cohorts (ER <1%, 1-10%, 11-70% and 71-100%) that were unique in Nottingham grade, nuclear grade, progesterone receptor expression and disease-free survival. Of the 341 patients with follow-up data, we found no significant differences in pathological features between patients in the ER 11-50% and ER 51-70% subgroups. These data support the important role of ER in breast cancer, and the importance of accurate testing and quantitative reporting for ER. Tumours with ER 1-10% are not common, and further studies are needed to understand more clearly this subgroup of breast cancer.

Abstract P6-06-08: Impact of initial surgical treatment delay on survival according to hormone responsiveness in breast cancer

Abstract Previous studies on the issue of the prognostic importance of treatment delay in breast cancer have shown inconsistent results. Furthermore, the association between the impact of treatment delay and molecular characteristics of tumors has not been adequately addressed. The purpose of this study is to examine the prognostic impact of initial surgical treatment delay after biopsy-proven cancer diagnosis in breast cancer patients. A total of 1,393 consecutive invasive breast cancer patients, treated in Seoul National University Hospital, Seoul, Korea, between July 2006 and June 2008, were included in this study. Patients with in situ or metastatic carcinoma at the time of diagnosis and patients in whom the dates of the initial pathologic diagnosis were unknown were excluded. The median time from biopsy-confirmed cancer diagnosis to initial surgical treatment was 25 days (range 0-134). When the patients were classified according to their treatment delay days (0 to 29, 30 to 59, and ≥60days), there was no difference in survival between ‘0-29days’ group and ‘30-59days’ group. However, for patients who experienced more than 60 days of initial delay in surgical treatment, the survival was significantly worse when compared to other groups (p = 0.034). The association between the treatment delay and poor outcome was only seen in patients with ER and PR negative tumors (p = 0.018) while patients with hormone-responsive tumors showed no such association. Patients with ER and PR negative tumors developed more recurrence and had shorter disease-free survival if they had treatment delay of more than 60 days. The prognostic importance of treatment delay of more than 60 days remained significant in predicting disease-free survival after adjusting for other known prognostic factors such as age, tumor size, nodal status, cancer stage, nuclear grade and Ki-67 expression (HR 5.127; 95% CI, 1.350 to 19.472; p = 0.016). Our results suggest that having treatment delay of more than 60 days is associated with poor treatment outcome in patients with ER and PR negative breast cancer. Citation Information: Cancer Res 2013;73(24 Suppl): Abstract nr P6-06-08.

Predicting Breast Cancer Recurrence Following Breast-Conserving Therapy: A Single-Institution Analysis Consisting of 764 Chinese Breast Cancer Cases

The purpose of this study was to identify prognostic factors related to recurrence in women treated with breast-conserving surgery (BCS) and to predict the recurrence following breast-conserving therapy (BCT) by constructing a prediction model. The retrospective analysis included 764 consecutive invasive breast cancer patients treated with BCT in Shanghai Cancer Center between 1995 and 2008. Univariate and multivariate analysis were performed to identify independent risk factors for locoregional recurrence (LRR) and all the recurrence events. Logistic regression was used to construct a recurrence prediction model, which was further evaluated by receiver operating characteristics (ROC) curves. The 5-year locoregional recurrence-free survival (LRRFS) and recurrence-free survival (RFS) rates were 90.8 and 88.4%, respectively. Multivariate analysis revealed 1 independent predictive factor for LRRFS (lymph node, P=.0049) and three independent predictive factors for RFS (lymph node, P=.0036; molecular subtype, P=.0021; histological grade, P=.041). These three variables entered into logistic regression to establish a recurrent prediction model. ROC curve showed that the area under the curve (AUC) of the established model was 0.70 (95% confidence interval: 0.61-0.78). This model could classify patients into "high-risk recurrence" and "low-risk recurrence" groups and could successfully predict their prognosis (P<.00001). The information of lymph node status, molecular subtype, and grade may help doctors to evaluate recurrence risk of a woman treated with BCT. Our new model might be helpful in clinical practice for recurrence prediction after BCT in Chinese patients, though further validation studies are needed.

MC1R common variants, CDKN2A and their association with melanoma and breast cancer risk

We sought to examine the association between MC1R variants and the risk of melanoma and breast cancer in Polish population. We also determined the prevalence of compound heterozygous carriers of MC1R and CDKN2A (A148T) variants. We examined 500 unselected melanoma cases, 511 consecutive invasive breast cancer patients, 800 newborns, 421 healthy adults matched for sex and age with the melanoma cases and 511 healthy women matched for sex and age with the breast cancer cases. A statistically significant association of all 4 MC1R variants with the melanoma risk was found. For the R151C variant p value was 0.000008 and odds ratio 2.9; for the V60L variant p value was 0.007 and OR 1.78; for the R160C p was 0.006 and OR 1.76; for the R163Q p was 0.015 and odds ratio 2.1. None of the compound heterozygotes were significantly over-represented among any of the melanoma cases, the highest OR (4.2) observed in patients harbouring the A148T variant in CDKN2A and the R151C variant in MC1R. Positive association was found between carrying any of the MC1R variants and (i) increased occurrence of melanoma among I degree relatives of the carriers; (ii) increased occurrence of melanoma on UV-non-exposed skin areas. We also observed a tendency of increased risk of multiple melanomas among carriers of MC1R variants. The haplotype analysis demonstrates that MC1R variants do not co-occur in cis, compound carriers have both alleles affected. We found no association with the MC1R variants and breast cancer risk. In conclusion, the results of this population-based study show herein that MC1R variants are associated with increased melanoma risk in the Polish population. The risk of disease seems to be increased additively for patients harbouring also the CDKN2A common variant A148T.

The impact of axillary lymph nodes removed in staging of node-positive breast carcinoma

Number of positive lymph nodes in the axilla and pathologic lymph node status (pN) have a great impact on staging according to the current American Joint Committee on Cancer staging system of breast carcinoma. Our aim was to define whether the total number of removed axillary lymph nodes influences the pN and thus the staging. The records of 798 consecutive invasive breast cancer patients with T1-3 tumors and positive axillary lymph nodes who underwent modified radical mastectomy between 1999 and 2005 in our hospital were reviewed. The total number of removed nodes were grouped, and compared with the patient and tumor characteristics and the influence of the number of nodes removed on the staging was analyzed. The proportion of patients with > or =4 positive nodes (59%), and pN3 status (51%) were the highest in the group with 21-25 nodes removed. Compared with patients with 1-20 nodes removed, the proportion of patients with > or =4 positive nodes (52%), and pN3 status (46%) were significantly higher in those with more than 20 nodes removed. Although the proportion of Stage IIA and IIB decreased, the proportion of Stage IIIA and IIIC increased in patients with >20 nodes removed compared with those with 1-20 nodes removed. In patients with axillary node-positive breast carcinoma, staging is highly influenced by total number of removed nodes. Levels I-III axillary dissection with more than 20 axillary lymph nodes removed could lead to more effective adjuvant chemotherapy and increases substantially the proportion of patients to receive radiotherapy.

Prognostic significance of total number of nodes removed, negative nodes removed, and ratio of positive nodes to removed nodes in node positive breast carcinoma

Background This study was undertaken to investigate whether total number of nodes (pNtot) removed, negative nodes removed (pNneg), and ratio of positive nodes to total nodes removed (pNratio) are predictors of survival in node positive patients. Study design The records of 801 consecutive invasive breast cancer patients with T1-3 tumour and positive axillary lymph node who underwent modified radical mastectomy in our hospital were reviewed. pNtot and pNneg were categorized, and pNratio was computed. The influence of these probable prognostic factors on survival was investigated. Survival curves were generated by Kaplan–Meier method and log-rank test was used for comparisons. Multivariate analyses were performed by Cox proportional hazard model. Results Median pNtot, and pNneg are 19 (range 5–54), and 13 (range 0–53), respectively. pNtot > 15, and pNneg > 15 were independently associated with reduced hazard ratios (HRs) of 0.62 (CI 0.48–0.79), and 0.68 (CI 0.52–0.89), respectively. The highest ratio (>0.25) of pNratio is associated with the highest hazard ratio for death (HR 3.8, CI 2.74–5.50) compared to the lowest ratio for death (<0.001). Conclusions pNtot, pNneg, and pNratio appear prognostic factors for survival in node positive breast cancers. Axillary lymph node dissection with more number of nodes removed (>15) or negative nodes (>15) are associated with increased survival.

Prediction of supraclavicular lymph node metastasis in breast carcinoma

Purpose : Supraclavicular lymph node metastasis in breast cancer patients has a poor prognosis, and aggressive local treatment has usually resulted in severe morbidity. The purpose of this study was to select high-risk neck metastasis patients for prophylactic radiotherapy. Methods : Between 1990 and 1998, 2658 consecutive invasive breast cancer patients underwent surgery and adjuvant therapy in the hospital. The median age was 47 years (range 22–92). The median follow-up period was 39 months. The following factors were analyzed: age, tumor size, tumor location, histologic type, histologic grade, estrogen and progesterone receptor status, DNA flow cytometry study results, number of positive axillary lymph nodes, use of chemotherapy, radiotherapy, and/or hormonal therapy, and level of involved axillary nodes. Results : Of the 2658 patients, 113 (4.3%) developed supraclavicular lymph node metastasis during this period. Young age (≤40 years), tumor size >3 cm, high histologic grade, angiolymphatic invasion, negative estrogen receptor status, synthetic phase fraction >4%, >4 positive nodes, and level II or III involved nodes were all significant for predicting neck metastasis in the univariate analysis. Three predictive factors were significant after multivariate analysis: high histologic grade, >4 positive nodes, and axillary level II or III involved nodes. In patients with axillary level I involved nodes and ≤4 positive nodes, the incidence was 4.4%. If axillary level III was involved, the rate of supraclavicular lymph node metastasis was 15.1%. Conclusion : The incidence of supraclavicular lymph node metastasis was higher in the groups with >4 positive nodes and in those with axillary level II or III involved nodes. Selective use of comprehensive radiotherapy for these high-risk patients will achieve good locoregional control.

At convenience and systematic random sampling: effects on the prognostic value of nuclear area assessments in breast cancer patients

This study compares the influence of two different nuclear sampling methods on the prognostic value of assessments of mean and standard deviation of nuclear area (MNA, SDNA) in 191 consecutive invasive breast cancer patients with long term follow up. The first sampling method used was 'at convenience' sampling (ACS); the second, systematic random sampling (SRS). Both sampling methods were tested with a sample size of 50 nuclei (ACS-50 and SRS-50). To determine whether, besides the sampling methods, sample size had impact on prognostic value as well, the SRS method was also tested using a sample size of 100 nuclei (SRS-100). SDNA values were systematically lower for ACS, obviously due to (unconsciously) not including small and large nuclei. Testing prognostic value of a series of cut off points, MNA and SDNA values assessed by the SRS method were prognostically significantly stronger than the values obtained by the ACS method. This was confirmed in Cox regression analysis. For the MNA, the Mantel-Cox p-values from SRS-50 and SRS-100 measurements were not significantly different. However, for the SDNA, SRS-100 yielded significantly lower p-values than SRS-50. In conclusion, compared with the 'at convenience' nuclear sampling method, systematic random sampling of nuclei is not only superior with respect to reproducibility of results, but also provides a better prognostic value in patients with invasive breast cancer.

Receptor heterogeneity of human breast cancer as measured by multiple intratumoral assays of estrogen and progesterone receptor

Multiple intratumoral tissue samples from the primary mass of 30 consecutive invasive breast cancer patients were assayed for estrogen receptor (ER) and progesterone receptor (PR) by the dextran-coated charcoal method following frozen section histopathological examination. Steroid receptor status of each sample was classified as positive (R+) or negative (R−), based only upon quantitative guide lines form the ER/PR results. Four out of 32 (12.5%) of the invasive cancers had an intratumoral sample classified as R+ and one sample as R−. R+ invasive ductal carcinomas has a highly significant degree of tubule formation ( P = 0.005) when compared with R− invasive ductal cancers. While the quantitative ER content ( r = 0.18) and the degree of quantitative variation in ER content ( P = 0.04) did not correlate with the tumor cellularity of the individual samples, tumor cellularity ( P = 0.005) and ER content ( P = 0.005) were lower in the samples from the tumor border than from the central tumor samples. Variations in ER and PR content may be found on a regional basis within a breast tumor mass resulting from heterogeneity of tumor subpopulations and/or differences in tumor cellularity.