Neoadjuvant Chemotherapy In Breast Carcinoma Research Articles

Cutaneous myeloid sarcoma following neoadjuvant chemotherapy for breast carcinoma

<p>Myeloid sarcoma (MS) is a neoplasm composed of myeloid blasts occurring outside the bone marrow, most often found simultaneously, or after a diagnosis of acute myeloid leukemia. Very rarely, de novo MS has been diagnosed in patients with a prior history of non-hematolymphoid neoplasms treated with systemic chemotherapy. We report a case of a MS in a 43-year-old woman, 6 months after the diagnosis of a HER2+ breast carcinoma, treated with neoadjuvant chemotherapy. Chemotherapy drugs could have played a pathogenic role in the development of MS in this patient. The exceeding rarity of such cases does make further and broader studies fundamental, in order to clarify if and which chemotherapy drugs may be the cause of MS.</p>

Metformin with standard neoadjuvant chemotherapy in breast carcinoma

Abstract Background Breast cancer is the most common cancer among women which increases after the age of 35 till it reaches a peak at 55-64 years. Metformin is a synthetic oral biguanide that has been shown to cause a 30% reduction in the lifetime risk of all cancers in diabetic patients on Metformin. We aimed at evaluating this antineoplastic effect in terms of pathological response, concurrent with standard neoadjuvant chemotherapy in breast cancer. Methodology 60 non-diabetic breast cancer patients receiving standard neoadjuvant chemotherapy at the breast cancer outpatient clinic, Ain Shams University hospital, were randomized into two arms (30 in each arm); Arm A Group receiving Metformin (850 mg bid) with standard line of neoadjuvant chemotherapy (FEC/Taxotere +/- Herceptin). Arm B Control group receiving the standard line of neoadjuvant chemotherapy alone. Results There’s a significant difference between Metformin and control arm in terms of response (complete and partial) versus no response (p = 0.03). Response to Metformin was significantly more pronounced in Luminal B subtype breast cancer (p = 0.03) and in grade II (p = 0.03). There’s no significant difference in toxicity between both arms; most common toxicities in both arms were vomiting (53.6%), nausea (30.4%) and neutropenia (30.4%) Conclusion Metformin has a significant antineoplastic effect which was measured in this study in terms of significant increase in pathological response concurrently with neoadjuvant chemotherapy in breast cancer compared to giving neoadjuvant chemotherapy alone.

A Study on Clinical and Pathological Responses to Neoadjuvant Chemotherapy in Breast Carcinoma.

Aim and objectivesTo assess the effectiveness of neo-adjuvant chemotherapy and its impact on the clinical and pathological response in locally advanced breast cancer. To compare molecular subtypes of breast cancer with response to neo-adjuvant chemotherapy.Patients and methodsThis was a prospective study on patients who received neoadjuvant chemotherapy for breast carcinoma for a 3-year period. A total of 60 patients who presented with locally advanced breast cancer (LABC) were treated with neoadjuvant chemotherapy. Forty patients were treated with the 5-fluorouracil, epirubicin, and cyclophosphamide (FEC) schedule, 16 patients were treated with Adriamycin and cyclophosphamide (AC), and four patients were treated with oral cyclophosphamide, intravenous methotrexate, and fluorouracil (CMF). Taxol was added in all node-positive cases, triple negative breast cancer (TNBC), and Her 2 positive cases. The clinical response was assessed with RECIST criteria after neoadjuvant chemotherapy. The response was compared with molecular subtypes of carcinoma breast and receptor status individually.ResultsA total of 60 female patients receiving primary chemotherapy for locally advanced breast malignancy were studied. The median age of the patients at the time of diagnosis was 44 years (range=24–73). In terms of menopausal status, 25 (42%) patients were pre-menopausal and 35 (58%) patients were post-menopausal. Histological classification showed invasive ductal carcinoma in 72% of patients, invasive lobular carcinoma in 15% of patients, and other types including mixed patterns in 13% of patients. Among 60 patients, 16 patients (26.6%) had clinically complete remission (cCR), 30 patients (50%) had partial remission, eight patients (13.3%) had stable disease, and six patients (10%) had progressive disease. Following neoadjuvant chemotherapy, 46 (76.6%) patient underwent Modified radical mastectomy surgery. Target therapy was given for Her2 neu patients after surgery. Hormonal therapy was added to hormone ER PR positive cases postoperatively. Eight patients (13.3%) among this operated cases attained complete pathological response.ConclusionPreoperative chemotherapy downstages the primary tumors and axillary metastasis in patients with locally advanced breast carcinoma. Comparison of molecular subtypes with chemotherapy response is a better way to find out the predictors of response to chemotherapy.

PTEN and PARP1 expression as predictors of neoadjuvant chemotherapy response in breast cancer: A case-control study

Background: Most breast cancer patients in developing countries present at an advanced stage and require neoadjuvant chemotherapy (NACT) before mastectomy. Chemotherapy in breast cancer generally kills cancer cells via apoptotic mechanisms, and chemotherapy response could be predicted by assessing biological markers associated with apoptosis, including phosphatase and tensin homolog deleted on chromosome ten (PTEN) and Poly-ADP-ribose polymerase 1 (PARP1). Objective: This study investigated the correlation between PTEN and PARP1 expression and NACT response in breast carcinomaMethods: Breast carcinoma patients who received NACT in 2017-2018 were consecutively selected, consist of 22 patients with positive NACT response and 22 patients with negative NACT response. Immunohistochemical examination of PTEN and PARP1 was carried out, and their expression was categorized with high and low PTEN expression and high and low PARP1 expression. Statistical analysis using chi-square test was performed to assess the relationship between clinicopathological characteristics, PTEN expression, PARP1 expression, and response to NACT. The significance test was determined at p <0.05.Results: There was a significant relationship between tumor size (p=0.030) and PTEN expression (p=0.035) with the response to NACT in breast carcinoma. Low PTEN expression had a risk of negative clinical response to NACT by 3.754 times compared to breast cancer with high PTEN expression. Meanwhile, there was no significant relationship between PARP1 expression and response to NACT in breast carcinoma.

Review of Outcomes in North East England for Patients Receiving Neoadjuvant Chemotherapy for Breast Carcinoma

Purpose: Neoadjuvant chemotherapy can allow for breast conserving surgery to be undertaken and for assessment of tumour response to therapy, inferring prognostic implications. We reviewed outcomes for all patients receiving neoadjuvant chemotherapy, in terms of pathological complete response (pCR) rates, to see if these were comparable with published data [1].

The role of PD-L1 in the prediction of treatment responses to neoadjuvant chemotherapy in breast carcinoma

Aims: To assess programmed death ligand 1 (PD-L1) expression and its correlation with prediction of response to neoadjuvant chemotherapy (NACT) in invasive breast carcinoma (IBC). Introduction: NACT is being increasingly utilised in IBC management with pathologic complete response (pCR) strongly correlated with excellent disease-free and overall survival. PD-L1 has recently gained attention in breast carcinomas as a potential therapeutic target as well as a prognostic indicator. PD-L1 is expressed in response to inflammation and has been found to be expressed on a number of tumours. The presence of tumour infiltrating lymphocytes has been found to be strongly associated with pathological complete response (pCR) and a relationship between PD-L1 and pCR has been suggested in recent studies. Methods: Pretreatment core biopsies and their matched subsequent surgical excision from 74 consecutive patients with IBC from the PathWest pathology database, Fiona Stanley Hospital, in 2013–2016 were assessed for TILs and PD-L1 expression. Results: Eighteen cases achieved pCR while 56 cases did not. When comparing these groups, there was a greater likelihood of pCR in patients with higher TILs scores (p=0.006) and higher PD-L1 scores (p=0.018). Conclusion: Our study demonstrates a significant association between PD-L1 expression with pCR in NACT.

A study on clinico-pathological assessment of response to neoadjuvant chemotherapy in breast carcinoma.

Neoadjuvant chemotherapy (NACT) has become a strategy in the multidisciplinary treatment approach to breast cancer. Since clinical and radiological responses do not correlate well with residual tumor after treatment, pathological evaluation of tumor response to chemotherapy is essential for accurate assessment. The aim of this study is to assess clinicopathological response to NACT in patients with invasive breast carcinoma. Single institution, retrospective study was conducted for 4 years. The study included 95 cases with the clinical diagnosis of locally advanced breast cancer and invasive breast carcinoma on histopathological examination of core needle biopsy/lumpectomy specimen. These cases were assessed for estrogen, progesterone, and human epidermal growth factor receptor 2 (HER2) receptors and treated with four cycles of NACT (adriamycin-cyclophosphamide) therapy. Histopathological examination of postchemo modified radical mastectomy specimens was performed following standard protocol. The pathological response of tumor to chemotherapy was assessed on Miller-Payne grading (MPG) and residual disease in breast and lymph node (RDBN) level. Data were analyzed in percentages and presented in charts and tables. Histopathological examination of pre-chemo biopsy specimens revealed invasive ductal carcinoma No special type (NST) in maximum, 89 (93.7%) cases. Majority 43 (45.3%) cases were HER2-positive followed by estrogen receptor-positive and/or progesterone receptor positive and HER2-positive type seen in 23 (24.2%) cases and 22 (23.1%) cases were triple negative. Sixteen (16.8%) and 76 (80%) cases showed pathological complete response (pCR) and partial pathological response, respectively, to NACT on MPG; 12 (12.6%) and 83 (87.4%) cases showed pCR and residual disease, respectively, on RDBN level. Majority 37.5% and 50% of cases showing pCR on MPG and RDBN level, respectively, were triple negative. This study highlights the clinicopathological response to NACT in carcinoma breast patients and identifies the molecular subtypes of these patients likely to respond to NACT.

Accuracy of Intraoperative Frozen Section of Sentinel Lymph Nodes After Neoadjuvant Chemotherapy for Breast Carcinoma.

False-negative (FN) intraoperative frozen section (FS) results of sentinel lymph nodes (SLN) have been reported to be more common after neoadjuvant chemotherapy (NAC) in the primary surgical setting. We evaluated SLN FS assessment in breast cancer patients treated with NAC to determine the FN rate and the histomorphologic factors associated with FN results. Patients who had FS SLN assessment following NAC from July 2008 to July 2017 were identified. Of the 711 SLN FS cases, 522 were negative, 181 positive, and 8 deferred. The FN rate was 5.4% (28/522). There were no false-positive results. Of the 8 deferred cases, 5 were positive on permanent section and 3 were negative. There was a higher frequency of micrometastasis and isolated tumor cells in FN cases (P<0.001). There was a significant increase in tissue surface area present on permanent section slides compared with FS slides (P<0.001), highlighting the inherent technical limitations of FS and histologic under-sampling of tissue which leads to most FN results. The majority (25/28, 89%) of FN cases had metastatic foci identified exclusively on permanent sections and were not due to a true diagnostic interpretation error. FN cases were more frequently estrogen receptor positive (P<0.001), progesterone receptor positive (P=0.001), human epidermal growth factor receptor-2 negative (P=0.009) and histologic grade 1 (P=0.015), which most likely reflects the lower rates of pathologic complete response in these tumors. Despite its limitations, FS is a reliable modality to assess the presence of SLN metastases in NAC treated patients.

Thermo Mammogram as a Tool to Assess Response to Neoadjuvant Chemotherapy in Breast Carcinoma

Abstract Introduction: Response to neoadjuvant chemotherapy (NACT) is predicted by clinical examination alone in locally advanced breast carcinoma. This study uses thermo mammogram (TMG) to assess the response. Aim and Objectives: The aim is to study TMG changes during NACT in breast cancer and predict response to NACT in locally advanced carcinoma and to compare clinical response with TMG response/changes in any form. Patients and Methods: All patients with locally advanced breast cancer who had treated with NACT were included in this study. Baseline TMG picture was taken using illumina360° (digital robotic rotational thermography device for 360 degree view of each breast) system before chemotherapy. TMG was repeated before next cycle. All patients were also assessed clinically during and after each cycle of chemotherapy. To assess the potential of TMG in predicting tissue response to chemotherapy, the precool, postcool, and the temperature difference between precool and postcool before every cycle were analyzed. Results: A total of 19 patients were analyzed. Eight patients had complete clinical response, six patients had partial response, and five patients had static disease. Median of precool, temperature difference between precool and postcool for patients between no response and complete response did not show statistically significant difference. However, the median of postcool spot temperature showed statistically significant difference. Median of postcool temperature difference for patients between partial response and complete response showed statistically significant difference. The median of postcool spot temperature for patients with no response and partial response did not show statistically significant difference. Precool temperature difference for all the visits showed no statistically significant difference. Conclusion: This preliminary study suggests that the TMG has potential for monitoring NACT response in breast cancer patients. Postcool temperature measurement is an early indicator of response to NACT.

Predictors of Pathological Complete Response in Women with Clinical Complete Response to Neoadjuvant Chemotherapy in Breast Carcinoma

Objective: There is insufficient information on predictors of pathologic complete response (pCR) to neoadjuvant chemotherapy (NAC) in breast carcinoma that also presented clinical complete response (cCR) evaluated in breast, axilla and breast and axilla. Methods: This retrospective study included 310 women with breast carcinoma who received NAC from 1/1/13 to 12/31/15 with follow-up until 8/31/16. The factors analyzed to predict pCR and cCR were menopausal status, Ki67, estrogen receptor, histologic grade, molecular subtype, tumor size, axilla status, and stage. Results: The cCR/pCR rates were 53.2/16.5% (breast), 76.3/36.8% (axilla) and 50.6/13.9% (breast and axilla). Molecular subtype and HER2-positive were independent predictors to confirm pCR in women with cCR, mainly triple negative (TN) in breast (OR 22.81, 95% CI 7.13–72.96) and breast and axilla (OR 36.06, 95% CI 8.77–148.26), but not in axilla. Ki67 ≥50% expression was predictor of cCR in breast (OR 2.00, 95% CI 1.31–3.06) and breast and axilla (OR 1.67, 95% CI 1.10–1.45). Conclusion: TN subtype and HER2-positive were the main independent predictors of pCR in women who also had cCR to NAC in breast and breast and axilla, but none was predictor in axilla. The Ki67 ≥50% was the independent predictor of cCR in breast and breast and axilla.

DCE-MRI and parametric imaging in monitoring response to neoadjuvant chemotherapy in breast carcinoma: a preliminary report.

PurposeNeoadjuvant chemotherapy is recommended in patients with locally advanced breast cancer. Dynamic contrast-enhanced magnetic resonance imaging (DCE-MRI) enables evaluation of the tumour neovasculature that occurs prior to any volume change, which helps identify early treatment failures and allows prompt implementation of second-line therapy.Material and methodsWe conducted a prospective study in 14 patients with histopathologically proven breast cancer. DCE-MRI data were acquired using multisection, T1-weighted, 3D vibe sequences with fat suppression before, during, and after IV bolus injection (0.1 mmol/kg body weight, Gadoversetamide, Optimark). Post-processing of dynamic contrast perfusion data was done with the vendor’s Tissue 4D software to generate various dynamic contrast parameters, i.e. Ktrans, Kep, Ve, initial area under the time signal curve (IAUC), apparent diffusion coefficient (ADC), and enhancement curve. Patients underwent MRI examinations at baseline, and then after two cycles, and finally at completion of chemotherapy.ResultsBased on Sataloff criteria for pathological responses, four patients out of 14 were responders, and 10 were non-responders. At the 2nd MRI examination, IAUC was significantly smaller in responders than in non-responders (p = 0.023). When the results of the first and second MRI examinations were compared, Kep decreased from baseline to the second MRI (p = 0.03) in non-responders and in responders (p = 0.04). This change was statistically significant in both groups. The ADC values increased significantly in responders from baseline to the third MRI (p = 0.012).ConclusionsIn our study, IAUC and ADC were the only parameters that reliably differentiated responders from non-responders after two and three cycles of chemotherapy.

Changes in Pathological Complete Response Rates after Neoadjuvant Chemotherapy for Breast Carcinoma over Five Years.

Historically, neoadjuvant chemotherapy (NACT) was extrapolated from adjuvant regimens. Dual HER2 blockade and the introduction of carboplatin for triple negative breast cancers (TNBC) emerged by December 2013 and have improved pathological complete response (pCR) rates. The objective of this study was to assess the pCR rates before and after the introduction of these new neoadjuvant regimens. Materials and Methods. Stage I–III breast cancer patients who received NACT were analyzed for rates of pCR by clinical characteristics (i.e., age, BMI, axillary lymphadenopathy, and histologic subtype), by time period (1 = 3/2010–11/2013, 2 = 12/2013–3/2015), and by type of chemotherapy (e.g., anthracycline/taxane only, carboplatin-containing, and HER2 blockade). Results. 113 patients received NACT. Overall pCR rate was 26.5 percent (n = 30). The pCR rate increased from 14% to 43.1% (p = 0.001) from time period 1 to time period 2 and were associated with HER2 positivity (p = 0.003), receiving treatment during time period 2 (p = 0.001) and using an anthracycline/taxane plus additional agent type of regimen (p = 0.004). Conclusions. Our study revealed a significant difference in rates of pCR over five years. Window of opportunity trials and other trials that utilize pCR analysis should be encouraged.

Pathological Complete Response and Changes Related to T Infiltrating Lymphocytes and Regulatory T Cells in Tissue and Peripheral Blood After Neoadjuvant Chemotherapy in Breast Carcinoma

ABSTRACT Aim: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. In this context, tumor infiltrating lymphocytes (TILs) and regulatory Tcells (Tregs) in tissue specimens and in peripheral blood are being tested as two emerging prognostic and predictive factors. We designed a protocol to analyze immune profile before, during and after neoadjuvant chemotherapy (CT) in breast cancer in blood and tissue, and their eventual relation with pathological complete response (pCR). Methods: From March 2011 to february 2014, 47 patients (18 her2 + /29 her2-) with T2-4 N0-3 breast carcinoma treated wih neoadjuvant CT in the Breast Cancer Unit of the Hospital Universitario Virgen Macarena (Seville, Spain) were included in the study. CD3 + , CD8 + , CD8-16-56+ and FOXP3+ cell infiltrates were detected by immunohistochemistry before and after CT in tissue specimens. Blood samples were collected in EDTA-K3 tubes before every cycle to determine the immunophenotype profile. Cell populations were determined by flow cytometry analysis of whole blood, including the study of CD3-CD4-CD25low and CD3-CD4-C25high (regulatory) T cells. Results: By February 2014, 47 patients were operated. pCR or near pCR (grade 4/5 Miller&Payne) was attained in 20 patients (42,6%). pCR was achieved in 66,6% (12/18) of tumors overexpressing her2 and treated with CT plus trastuzumab, and in only a 27,5% (8/29) of the her2- population. Absence and /or disappearance of Tregs in tissue (Black grading system = 0) was more frequent after neoadjuvant CT (11,11 vs 62,2%). Furthermore, average whole blood CD3-CD4-CD25high (regulatory) T cells were 126,36 before and 91,19 after neoadjuvant CT (p 0,010). Overall Tregs diminished in the pCR and non pCR groups without statistically significant differences. Conclusions: Neoadjuvant CT decreases Tregs immunosuppressive infiltrates in tissue and CD3-CD4-CD25high (regulatory) T cells in peripheral blood in all the population. Although differences among subgroups (pCR/non-pCR and her-/her2+) were not statistically significant, these data support the role of Tregs as an interesting biomarker with eventual therapeutic implications in breast carcinoma. Disclosure: All authors have declared no conflicts of interest.

Pathologic complete response and changes related to T-infiltrating lymphocytes and regulatory T cells in tissue and peripheral blood after neoadjuvant chemotherapy in breast carcinoma.

e22073 Background: Some clinical trials in breast cancer have reported imppressive outcomes related to laboratory immune findings in the neoadjuvant setting. In this context, tumor infiltrating lymphocytes (TILs) and regulatory T cells (Tregs) in tissue specimens and in peripheral blood are being tested as two emerging prognostic and predictive factors. We designed a protocol to analyze specifically TILs before, during and after neoadjuvant chemotherapy (CT) in breast cancer in blood and tissue, and their eventual relation with pathological complete response. Methods: From March 2011 to January 2013, 48 patients (18 HER2+/ 30 HER2-) with T2-4 N0-3 breast carcinoma treated with neoadjuvant chemotherapy in the Breast Cancer Unit of the Hospital Universitario Virgen Macarena (Seville, Spain) were included in the study protocol. CD3+, CD8+, CD8-16-56+ and Foxp3+ cell infiltrates were detected by immunohistochemistry before and after the end of neoadjuvant chemotherapy in tissue specimens. Blood samples were collected in EDTA-K3 tubes before every cycle of CT to determine the immunophenotype and regulatory cell profile. Cell populations were determined by flow cytometry analysis of whole blood. Results: By January 2013, 35 patients (11 HER2+/ 24 HER2-) were operated. Pathological complete responses (pCR) or near pCR (grade 4/5 Myller and Payne) were attained in 13 patients. pCR was achieved in 63.63% (7 of 11) of tumors overexpressing HER2, but in only a 25% (6 of 24) of HER2-negative tumors. Overall Tregs diminished in the pCR and non pCR groups. Disappearance of Tregs (Black grading system) was more frequent in the pCR group (69.23 vs 54.54%) and HER2+ population (63.63 vs 58.53%), although differences were not statistically significant. CD8+ infiltrates remain stable during treatment. Conclusions: Neoadjuvant CT decreases Tregs immunosuppressive infiltrates with no changes in CD8+ cytotoxic lymphocytes. Changes observed in lymphocytic infiltrates during neoadjuvant treatment indicate that Tregs may represent an interesting therapeutic target in breast carcinoma.

Expression of Immunohistochemical Markers before and after Neoadjuvant Chemotherapy in Breast Carcinoma, and Their Use as Predictors of Response

PurposeFor patients with breast carcinoma, immunohistochemical markers are important factors in determining the breast cancer subtype and for establishing a therapeutic plan, including the use of neoadjuvant chemotherapy (NACT). However, it is not clear whether the expression of certain markers changes after NACT.MethodsWe assessed estrogen receptor (ER), progesterone receptor (PR), human epidermal growth factor receptor 2 (HER2), Ki-67, p53, and Bcl-2 expression in specimens from 345 breast cancer cases before and after NACT. We analyzed the association between response to NACT and the expression of the markers in pre-NACT specimens. We also compared the expression between pre- and post-NACT specimens.ResultsER and PR expression was negatively associated with pathological complete response (pCR). HER2 was associated with pCR in all cases, but the association was lost when the cases were subdivided according to hormone receptor status. The pre-NACT tumor size of cases with pCR after NACT was smaller than that of cases with residual disease. HER2-enriched and triple-negative breast cancers were more likely to achieve pCR than luminal A type cancers. PR expression and the Ki-67 index decreased after NACT. A decrease in the Ki-67 index was also demonstrated in hormone receptor positive and HER2-enriched subtypes, but no similar tendency was observed in the triple-negative subtype.ConclusionA patient with breast cancer scheduled for NACT should be assessed for the breast cancer subtype, as this will influence the treatment plans for the patient. The expression of PR and Ki-67 after NACT should be interpreted carefully because NACT tends to reduce the expression of these molecules.

Positron emission tomography/computed tomography (PET/CT) as a biomarker of pathologic response to neoadjuvant chemotherapy in breast carcinoma.

e21147 Background: Pathological complete response (pCR) after neoadjuvant chemotherapy (NAC) in breast carcinoma is prognostic. Predictive biomarkers for pCR include early response to NAC, estrogen receptor (ER) negativity, HER2 positivity, and high Ki67. We assessed whether absence of fluoro-deoxy glucose (FDG) uptake measured by standardized uptake value (SUV) after NAC would predict pCR. Methods: We identified 23 patients (pts) who had PET/CT scanning pre and post NAC. We examined breast cancer subtype, chemotherapy (CT) regimen, number of cycles of CT given, clinical and pathological staging data and changes in SUV in the breasts and lymph nodes pre and post NAC. pCR was defined as no residual cancer in the breast or axillary lymph nodes. Results: Median age at diagnosis was 46 years (IQR; 37 to 56). Median tumor size at diagnosis was 30mm (IQR; 25 to 43) and 19 pts (83%) had node positive breast cancer. Most tumors were ductal (n=22) with 1 lobular cancer. Preoperatively 95% received all CT. All HER2+ pts received Trastuzumab. Anthracycline/taxane based regimens were most frequently given in 22 cases, 1 received lapatinib/trastuzumab. Five tumors (21.7%) were ER+/HER2+; 14 (60.9%) ER+/HER2-; 2 (8.7%) ER-/HER2+ and 2 (8.7%) were ER-/HER2-. All tumors were high (n=9, 39.1%) or intermediate grade (n=14, 61%). SUV was significantly lower post NAC (p=0.035). We observed no SUV uptake in breast or lymph nodes in 15 cases (65.2%) post NAC, these corresponded to; ER+HER2+ 4/5 (80%); ER+HER2- 7/15 (46.7%); ER-HER2- 2/2(100%), ER-HER2+ 2/2(100%). Absent SUV uptake post NAC was associated with a pCR (breast and lymph nodes) in 5/15 (33%) of pts (ER+HER2+ n=1, ER+HER2- n=1, ER-HER2- n=2, ER-HER2+ n=1). Ten of 15 tumors (67%) had no SUV uptake in the breast post NAC and 7 (47%) were associated with a pCR. There was a trend toward increased odds of pCR with no SUV uptake post NAC (OR 2.76; 95% CI 0.85 to 8.94: P= 0.09). Overall rate of pCR was 21.7% (n=5). Conclusions: A non-statistically significant trend toward increased odds of pCR with no SUV uptake post NAC was observed. Larger subtype-specific breast cancer cohorts will be required to determine the value of PET/CT as a predictive biomarker for pCR.

Increased efficacy of a dose-dense regimen of neoadjuvant chemotherapy in breast carcinoma: a retrospective analysis

Neoadjuvant chemotherapy is being increasingly used in the treatment of breast carcinoma. We performed a single-center retrospective analysis of the results of neoadjuvant therapy in 376 breast carcinoma patients treated with three different regimens combining doxorubicin and paclitaxel (AT), dose-dense doxorubicin and cyclophosphamide with sequential weekly paclitaxel (DD AC-P), or the combination of trastuzumab with chemotherapy (DD AC-PT). The expression of estrogen receptors (ER), progesterone receptors (PR) and human epidermal growth factor receptor (HER)-2 was determined immunohistochemically. Pathological response was determined in 318 patients. Pathological complete response (pCR) was observed in 18% of patients. The pCR rate was significantly higher in patients treated with DD regimen (22 vs. 13%) and younger than 55 years (23 vs. 13%). The pCR rate was higher in patients with triple negative (TN) tumors (43%) and tumors over-expressing HER-2 (HER-2+; 28%) compared to patients with ER- or PR-positive tumors not expressing HER-2 (ER/PR+HER-2-; 6%). In patients with TN tumors pCR rate was significantly higher after treatment with DD AC-P compared to AT (61 vs. 22%, p=0.005). pCR was associated with significantly improved relapse-free survival (RFS) and overall survival (OS), but when analysis was performed based on tumor phenotype, the difference was significant only in patients with TN tumors. In multivariate analysis, pCR, stage, and ER expression were significant predictors of RFS, while pCR, stage, ER and DD regimen were significant predictors of OS. In conclusion, present data indicate superiority of a DD regimen in obtaining pCR in patients with breast carcinoma treated with neoadjuvant chemotherapy. The difference in efficacy is due mostly to markedly higher pCR rate in patients with TN tumors.

False positive localisation of C-11 methionine in a colloid nodule

A 45-year-old female diagnosed with carcinoma of the left breast on histopathological examination underwent both 18F-flourodeoxyglucose (FDG) and 11C-methionine (MET) positron emission tomography/computed tomography (PET/CT) as part of a protocol comparing the utility of these tracers for predicting a response to neoadjuvant chemotherapy in breast carcinoma. Abnormal FDG and MET accumulation was noted in the left breast primary, left axillary lymph nodes, and also in a well-defined nodule present in the left lobe of the thyroid gland. Keeping in mind the possibility of thyroid neoplasm/metastasis, the patient was referred for fine needle aspiration cytology (FNAC) from the thyroid nodule that revealed features of a simple colloid nodule. Focal thyroid lesions incidentally found on 18F-FDG PET/CT have a high risk of thyroid malignancy. Non-specific accumulation of FDG in thyroid adenomas is also known. This case highlights a potential cause for false positive on C-11 MET PET/CT in colloid adenomas, which should be kept in mind while using this tracer for oncological indications.

Blood oxygen level-dependent MRI for the monitoring of neoadjuvant chemotherapy in breast carcinoma: initial experience

Purpose To determine the feasibility of using R2⁎ map MRI for pretreatment diagnosis and monitoring of tumor response to neoadjuvant chemotherapy (NAC) in patients with breast cancer. Material and Methods Twenty-eight women with breast cancer, as evidenced by pathology, underwent MR imaging prior to and after chemotherapy. All patients were examined by conventional MRI and R2⁎ map imaging. Subjects were divided into major histological response (MHR) and non-major histological response (NMHR) groups. Mean R2⁎ values of cancerous and normal glandular tissues were measured before and following NAC. Differences in R2⁎ and ΔR2⁎% values between these two groups were compared with paired or independent t tests. The relationship between ΔR2⁎% and histological response was examined using Spearman's correlation test. Results Before NAC, the average R2⁎ values in carcinoma were lower than in normal glandular tissue ( P<.05). After two to four cycles of NAC, the R2⁎ values in carcinoma were increased ( P<.05 ), but this change was not significant in normal glandular tissue. After NAC, ΔR2⁎% was significantly higher in MHR as compared to NMHR ( P<.05). The ΔR2⁎% correlated with the histological response ( r=0.581, P<.01). Conclusion In women undergoing NAC for breast cancer treatment, R2⁎ and ΔR2⁎% appear to provide predictive information of tumor response which is probably associated with changes in tumor angiogenesis and tissue oxygenation. R2⁎ map imaging of breasts may therefore be useful in monitoring tumor response to NAC.

Variations in Gene Expression and Response to Neoadjuvant Chemotherapy in Breast Carcinoma

In this study, we performed a screening of 266 gene expressions in breast carcinomas and carried out correlations with histological response to either FEC-100 (fluorouracil-epirubicin-cyclophosphamide; n = 16) or Tax-Epi (docetaxel-epirubicin; n = 12) treatment. Gene expression in biopsies obtained before and after one course of chemotherapy was analyzed. Expression of specific genes was significantly changed after one course of chemotherapy, particularly for Tax-Epi treatment. Comparison with histological response for both treatments revealed that only good responders exhibited changes in gene-expression profile. These results agree that expression of different genes changes in response to anthracycline-based neoadjuvant chemotherapy and show, for the first time, that response to docetaxel-based treatment implied also changes in gene-expression profile.