Does the degree of cell lesion in breast cancer after inductive chemotherapy have any prognostic value?

During 1991 and 1992, 77 patients with breast cancer were treated with induction chemotherapy using the CMFV and FAC protocols at the Lublin Oncological Centre. The degree of cancer cell damage in the specimens obtained postoperatively was evaluated by microscopy. Complete or substantial damage of neoplastic cells was found in 29% of the cases; whereas minimal to no damage was found in 71% of specimens. After assessing the 5-year survival periods of our patients in relation to the degree of cancer cell damage after induction chemotherapy, a statistically significant correlation was noted. Five-year survival without cancer symptoms was observed in 64% of cases in which the cell damage was estimated as considerable, and only in 34% in which the damage was slight or not notable. A much weaker correlation was observed between the degree of breast cancer cell damage after inductive chemotherapy and clinical response.     

Can breast MRI help in the management of women with breast cancer treated by neoadjuvant chemotherapy?

Contrast-enhanced (CE) MRI was used to monitor breast cancer response to neoadjuvant chemotherapy. Patients underwent CE MRI before and after therapy, together with conventional assessment methods (CAM). CE MRI was carried out at 1.5 T in the coronal plain with 3D sequences before and after bolus injection. An expert panel determined chemotherapy response using both CE MRI and CAM. Histopathological response in the surgical specimen was then used to determine the sensitivity and specificity of CE MRI and CAM. In total, 67 patients with 69 breast cancers were studied (mean age of 46 years). Tumour characteristics showed a high-risk tumour population: median size 49 mm: histopathological grade 3 (55%): oestrogen receptor (ER) negative (48%). Histopathological response was as follows: - complete pathological response (pCR) 17%; partial response (pPR) 68%; no response (NR) 15%. Sensitivity of CAM for pCR or pPR was 98% (CI 91-100%) and specificity was 50% (CI 19-81%). CE MRI sensitivity was 100% (CI 94-100%), and specificity was 80% (CI 44-97%). The absolute agreement between assessment methods and histopathology was marginally higher for CE MRI than CAM (81 vs 68%; P=0.09). In 71%, CE MRI increased diagnostic knowledge, although in 20% it was judged confusing or incorrect. The 2nd MRI study significantly increased diagnostic confidence, and in 19% could have changed the treatment plan. CE MRI persistently underestimated minimal residual disease. In conclusion, CE MRI of breast cancer proved more reliable for predicting histopathological response to neoadjuvant chemotherapy than conventional assessment methods.     

Clinicopathologic factors associated with false negative FDG–PET in primary breast cancer

Summary The present study was aimed to determine the clinicopathologic factors that predict false negative (FN) PET results in these patients.Methods A total of 116 breast lesions in 111 patients (pre-menopausal 45; perimenopausal 15; post-menopausal 51) with known or suspicious of breast cancer who underwent FDG–PET scans for staging, were included in this study. The median age was 52±11 years (range 32–79 years). All PET studies results were correlated with follow-up surgical pathology results. A cut off value of 2.5 was considered for positive or negative PET results. Univariate and multivariate analyses were performed to identify factors associated with FN results.Results Of 116 breast lesions, 85 were malignant and 31 were benign on histopathology. Of the 85 malignant lesions, 41 were true positive (TP) and 44 were FN. Among the 31 benign lesions, 30 were true negative and one was false positive. There was significant difference in the tumor size (p=0.003) and tumor grade (p=0.001) in patients with TP and FN PET results. Multivariate logistic regression demonstrated that tumor size (≤10 mm) and low tumor grade were independently associated with FN results. No significant relationship of FN PET results was found with age, menopausal status, tumor type, c-erbB-2, estrogen and progesterone receptors, sentinel lymph node or distant metastasis, parenchymal density and multifocality of primary breast tumor.Conclusion In present study, tumor size and tumor grade are independent factors that predict FDG–PET results. Smaller tumors (≤10 mm) and low-grade tumors are strong predictor of FN FDG–PET results.     

What is the role of neoadjuvant chemotherapy in the management of ovarian cancer?

Aggressive cytoreductive surgery followed by aggressive chemotherapy is the standard of care for advanced-stage ovarian cancer patients, among whom the greatest survival benefit is seen in those with no gross disease left after the initial surgical cytoreduction. Since this represents only 23% of stage III patients and 8% of stage IV patients, alternative strategies for patients who do not appear to be surgically cytoreducible to no macroscopic residual disease need to be identified. Neoadjuvant chemotherapy, which may offer a variety of benefits in this population, is one such strategy that is being evaluated in prospective randomized trials. This article reviews the current status of neoadjuvant chemotherapy for the management of women with advanced-stage ovarian cancer.     

αB-crystallin is a novel predictor of resistance to neoadjuvant chemotherapy in breast cancer

Aims αB-crystallin is an anti-apoptotic protein commonly expressed in poor prognosis basal-like breast tumors, which are largely triple (estrogen receptor (ER), progesterone receptor (PR), and HER2) negative. We examined whether αB-crystallin expression in breast cancer was associated with a poor response to neoadjuvant (preoperative) chemotherapy. Methods One hundred and twelve breast cancer patients who received neoadjuvant chemotherapy and who had post-chemotherapy tumor specimens available for analysis were included in the study. Forty-nine percent of patients were treated with doxorubicin and cyclophosphamide (AC), 37% received AC in combination with a taxane, and 14% received other regimens. Paired pre- and post-chemotherapy tumor specimens were available for 33 patients. αB-crystallin expression was determined by immunohistochemistry in tissue microarrays. Results Seventeen percent of tumors were αB-crystallin positive. αB-crystallin expression was identical in 32 of 33 cases for which both pre- and post-chemotherapy tumor tissue was available. αB-crystallin expression was associated with ER-negative (P = 0.0024) and triple negative status (P = 0.005). Overall response rates (ORR) defined as ≥50% reduction in tumor size after treatment were 53% (clinical ORR) and 61% (pathological ORR). Although tumor grade, size, ER, PR, HER2 or triple negative status was not associated with response, αB-crystallin-positive tumors had poorer overall response rates than αB-crystallin-negative tumors (clinical ORR, 21% vs. 59%, respectively, P = 0.0045; pathological ORR, 16% vs. 70%, respectively, P < 0.0001). Conclusion αB-crystallin is a novel biomarker expressed predominantly in triple negative breast tumors that identifies a subset of chemotherapy-resistant tumors, which may contribute to their poor prognosis.     

Effect of neoadjuvant anthracycline–taxane-based chemotherapy in different biological breast cancer phenotypes: overall results from the GeparTrio study

In order to explore the effect of neoadjuvant chemotherapy (NACT) on clinical mid-course and pathological complete response (pCR) at surgery in different biological breast cancer subtypes. The GeparTrio study included 2,072 patients with operable or locally advanced breast cancer. After two cycles with docetaxel, doxorubicin and cyclophosphamide (TAC) patients were randomized according to their clinical response. Clinical and biological factors were assessed for predicting clinically mid-course response and pCR at surgery. The overall pCR rate, defined as no invasive residuals in breast and axilla, was 20.5%. The highest pCR rate of 57% was observed in patients below 40 years of age with triple negative or grade 3 tumors. Independent factors for mid-course response and pCR were: young age, non-T4 tumors, high grade, and hormone receptor status, the strongest single predictive factor. Within the biological subtypes, grading was an independent factor to predict pCR for luminal tumors, clinical tumor stage for the HER2 like tumors and age for the triple negative ones. Grading gave independent information for mid-course response within the triple negative group. No factor predicted mid-course response within the other groups. Grading and age can identify subgroups within the luminal and triple negative patients who have an increased benefit from NACT.     

Does chemotherapy regimen matter in the neoadjuvant treatment of esophageal cancer?

BackgroundNeoadjuvant chemoradiotherapy has become the mainstay of treatment for locally advanced esophageal cancer. CALGB 9781 trial established cisplatin and 5-flourouracil (5-Fu) with radiotherapy as superior to surgery alone while the CROSS trial established paclitaxel, carboplatin, and radiotherapy as superior to surgery alone. Previous data has been unclear as to which regimen provides a superior pathologic response. This study aims to look at this. This study aims to look at this.MethodsA retrospective chart review at a single institution of patients who underwent esophagectomies after neoadjuvant chemoradiotherapy with either cisplatin and 5-Fu or carboplatin and paclitaxel between 2012–2020 was performed. Demographics as well as staging, response rates, and modified Ryan scores were collected. Univariate analysis between the two groups was performed.ResultsA total of 82 patients were identified between 2012–2020 who underwent esophagectomy after neoadjuvant chemoradiotherapy. In total, 74 (90.2%) received carboplatin and paclitaxel while 8 (9.8%) received 5-Fu and carboplatin. Both groups included patients with squamous cell carcinoma (SCC) and adenocarcinoma. No significant factors were found in terms of patient comorbidities or pathologic staging. There was no significant difference in modified Ryan score between the two groups (P=0.745).ConclusionsThis study evaluates the degree and presence of pathologic response between the two neoadjuvant chemoradiotherapy modalities used for esophageal cancer. Our results, in contrast to other studies, suggest no significant difference with regards to pathologic response rate. Furthermore, our findings suggest that use of the least toxic regimen would make sense.     

Can chemotherapy alter the course of prostate cancer?

Prostate cancer is perceived to be a disease of older men often diagnosed with widespread metastases that respond to hormonal ablation but for which there are few additional treatment options. Fortunately this perception is rapidly changing as newer combination chemotherapy trials demonstrate improved prostate-specific antigen and measurable response rates and enhanced quality of life. Still, treatment of prostate cancer lags behind treatment of other malignancies. Work remains in understanding the natural history of disease, refining our grouping of patients by stage into clinical trials, and adhering to new response criteria recently developed. Applying the newer active chemotherapy regimens to patients with earlier stage disease should lead to improvements in overall survival.     

Is lymphovascular invasion degree one of the important factors to predict neoadjuvant chemotherapy efficacy in breast cancer?

Background  

Patients who achieve pathologic complete response (pCR) after neoadjuvant chemotherapy (NAC) have favorable disease-free survival rates. A few studies have suggested that lymphovascular invasion degree may play an important role in predicting pCR. This study aims to confirm the role of lymphatic invasion degree in predicting pCR in breast cancer patients after NAC.     

Pre-chemotherapy 18F-FDG PET/CT upstages nodal stage in stage II–III breast cancer patients treated with neoadjuvant chemotherapy

In breast cancer patients treated with neoadjuvant chemotherapy (NAC) the number of tumor-positive nodes can no longer reliably be determined. Furthermore, ultrasound (US) seems suboptimal for the detection of N3-disease. Therefore we assessed the proportion of breast cancer patients treated with NAC in which pre-chemotherapy 18F-FDG PET/CT detected ≥4 axillary nodes or occult N3-disease, upstaging nodal status and changing risk estimation for locoregional recurrence (LRR). Conventional regional staging consisted of US with fine needle aspiration and/or sentinel lymph node biopsy. Patients were classified as low-risk (cT2N0), intermediate-risk (cT0N1, cT1N1, cT2N1, cT3N0), or high-risk (cT3N1, cT4, cN2–3) for LRR. The presence and number of FDG-avid nodes were evaluated and the proportion of patients that would be upstaged by PET/CT, based on detection of ≥4 FDG-avid axillary nodes defined as cN2(4+) or occult N3-disease, was calculated. In total, 87 of 278 patients were considered high-risk based on conventional staging. PET/CT detected occult N3-disease in 5 (11 %) of 47 low-risk patients. In 144 intermediate-risk patients, PET/CT detected ≥4 FDG-avid nodes in 24 (17 %) patients and occult N3-disease in 22 (15 %) patients, thereby finally upstaging 38 (26 %) of intermediate-risk patients. Of 43 (23 %) upstaged patients, 18 were ypN0, 12 were ypN1, and 13 were ypN2–3. Pre-chemotherapy PET/CT is valuable for selection of breast cancer patients at high risk for LRR. In our population, 23 % of patients treated with NAC were upstaged to the high-risk group based on PET/CT information, potentially benefiting from regional radiotherapy.     

Can we predict local recurrence in breast conserving surgery after neoadjuvant chemotherapy?

Background

One of the benefits of neoadjuvant chemotherapy (NAC) is its ability to convert patients ineligible for breast conservative treatment (BCT) to be candidates for this treatment, although questions have been raised regarding the effectiveness of BCT in terms of loco-regional recurrence (LRR). The objective of this study is to evaluate LRR in this group and the influence of tumor characteristics in recurrence.

Material and Methods

Between 1996 and 2007, 137 patients were treated with BCT after NAC at our Service. After completion of NAC a multidisciplinary team evaluated the cases eligible for BCT. All patients treated with BCT had negative margins and received radiation therapy. Risk factors associated with local recurrence were analyzed using Kaplan–Meier survival curves and long-rang test.

Results

Information was obtained in 121 patients. Median age was 54 years old (SD: 12 years). At a median follow-up of 35 months (range, 18–87 months), 6 (4.95%) patients developed an LRR, with an accumulative incidence at 5 years of 7.3% (95% CI: 0.4–14.1%) and at 10 years of 11.5% (95% CI: 2.8–20.1%). Overall survival at 5 and 10 years was 94.8% (95% CI: 90.9–98.6%) and 82.3% (95% CI: 67.3–97.2%) respectively. Tumor size (T3) (p < 0.001) and pathological stage (Stage III) (p = 0.001) after surgery were strongly associated with LRR.

Conclusions

The results of this study confirm that BCT is an effective treatment in patients with NAC. Tumor size and pathological stage after systemic treatment influence loco-regional recurrence in patients with BCT.     

Complete axillary conversion after neoadjuvant chemotherapy in locally advanced breast cancer: a step towards conserving axilla?

OBJECTIVES: This study was designed to assess the clinical, sonographic and histopathological response of axillary lymph node metastasis to neoadjuvant chemotherapy in patients with locally advanced breast cancer. MATERIAL AND METHODS: Forty patients with locally advanced breast cancer (LABC) with clinically palpable or sonographically detectable axillary nodes were studied. FNAC of the primary tumor and axillary nodes was done and patients were started on neoadjuvant chemotherapy. Axillary nodes were assessed clinically and sonographically for response after 3 cycles of chemotherapy. All patients underwent total mastectomy with axillary clearance and the lymph nodes in the specimen were examined for metastasis. RESULTS: 47% patients had complete clinical nodal response, while 19% showed complete sonographic response. Complete pathological nodal response was documented in 22% of patients. Ultrasonography was found to be more sensitive than clinical examination in assessing complete nodal response. 10% of the patients had complete pathological response of both primary tumor and axillary nodes. There was significant correlation between pathological response of primary tumor and lymph nodes (P=0.004). Patients with complete sonographic or clinical response were found to have no or minimal residual disease in axilla and hence axillary dissection may be avoided in them.     

FDG–PET for assessment of early treatment response after four cycles of chemotherapy in patients with advanced-stage Hodgkin's lymphoma has a high negative predictive value

Background: As positron emission tomography (PET) seems to be a powerful prognostic marker in the treatment of Hodgkin's lymphoma (HL), we analysed the prognostic value of PET after four cycles of combination therapy with bleomycin, etoposide, doxorubicin, cyclophosphamide, vincristine, procarbazine and prednisone (BEACOPP) in patients with advanced-stage HL.Patients and methods: From January 2004 to March 2007, 50 patients with newly diagnosed HL in clinical stages IIB with large mediastinal mass or extranodal disease, III and IV were treated according to the HD15 protocol of the German Hodgkin Study Group. All patients received a PET scan after four cycles of BEACOPP (PET-4).Results: Of the overall group, 14 of 50 patients had a positive PET-4 while 36 had a negative PET-4. At a median observation time of 25 months, 2 of the 14 patients with a positive PET-4 had progressed or relapsed, while there was no progression or relapse in PET-4-negative patients.Conclusion: Our results indicate a very good negative predictive value of PET-4 in advanced-stage HL patients treated with BEACOPP.