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.     

What is the current standard of care for anti-HER2 neoadjuvant therapy in breast cancer?

Neoadjuvant treatment with a sequential anthracycline-taxane-based chemotherapy in combination with trastuzumab (Herceptin) is currently a preferred therapy for patients with HER2-positive breast cancer. This approach is based on the higher pathologic complete response (pCR) of 40% seen with the addition of trastuzumab, compared with a 17% pCR with chemotherapy alone. The pCR can be increased to 75% with dual HER2-receptor blockade and chemotherapy. Higher pCR rates are found in hormone-receptor-negative tumors. Patients with a pCR after chemotherapy and trastuzumab showed a significantly better outcome compared with those who did not have a pCR. The need for additional or alternate treatment options is great in patients who do not achieve a pCR. Addition of lapatinib (Tykerb) or pertuzumab (Omnitarg) to trastuzumab is a therapeutic option. Recent findings suggest pCR might not be the appropriate surrogate for long-term outcome in patients with hormone receptor-positive and HER2-positive tumors.     

What is the future of magnetic nanoparticles in the axillary management of breast cancer?

Magnetic nanoparticles (MNPs) possess unique properties, which make them highly attractive for medical applications. The use of MNPs in surgery has mainly been focused on their role in the identification of metastatic lymph node involvement. There have been developments within this field, including ongoing and newly conducted clinical trials. The current published evidence for the use of MNPs in assessing metastatic lymph node spread using sentinel lymph node biopsy and non-invasive imaging modalities is reviewed and future applications considered.     

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.     

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.     

What is the current status of ovarian suppression/ablation in women with premenopausal early-stage breast cancer?

The role of ovarian suppression/ablation (OS/OA) in premenopausal women with hormone receptor-positive breast cancer has been evolving for more than a century. It is clear that OS/OA is an effective adjuvant therapy for these women, but despite numerous studies enrolling thousands of women, many unanswered questions remain. In particular, a major question is whether additional benefit is gained with combination treatment comprising luteinizing hormone-releasing hormone (LH-RH) agonists and tamoxifen over tamoxifen alone. Ongoing trials also are assessing the coupling of aromatase inhibitors (traditionally contraindicated in these patients because of paradoxic stimulation of estrogen production) and LH-RH agonists. Any potential disease-free or overall survival advantage of combination treatment must be balanced against a possible increase in adverse effects and impairment of quality of life. This review focuses on new data regarding how to incorporate OS/OA into the rational treatment of this challenging patient population.     

What is the current status of ovarian suppression/ablation in women with premenopausal early-stage breast cancer?

The role of ovarian suppression/ablation (OS/OA) in premenopausal women with hormone receptor-positive breast cancer has been evolving for more than a century. It is clear that OS/OA is an effective adjuvant therapy for these women, but despite numerous studies enrolling thousands of women, many unanswered questions remain. In particular, a major question is whether additional benefit is gained with combination treatment comprising luteinizing hormone-releasing hormone (LH-RH) agonists and tamoxifen over tamoxifen alone. Ongoing trials also are assessing the coupling of aromatase inhibitors (traditionally contraindicated in these patients because of paradoxic stimulation of estrogen production) and LH-RH agonists. Any potential disease-free or overall survival advantage of combination treatment must be balanced against a possible increase in adverse effects and impairment of quality of life. This review focuses on new data on how to incorporate OS/OA into the rational treatment of this challenging patient population.     

The efficacy and safety of neoadjuvant chemotherapy?+/??letrozole in postmenopausal women with locally advanced breast cancer: a randomized phase III clinical trial

This two-arm randomized clinical study aimed to evaluate the efficacy and safety of neoadjuvant concurrent chemotherapy and letrozole in postmenopausal women with locally advanced breast carcinoma. One hundred and one postmenopausal women aged 50-83 years with pathologically proven locally advanced (clinical stage T3, T4 and/or N2, N3) breast cancer were randomly assigned to receive neoadjuvant chemotherapy alone (control arm, n = 51) or neoadjuvant chemotherapy concurrent with letrozole 2.5 mg (study arm, n = 50). Chemotherapy consisted of a median 4 (range 3-5) cycles of intravenous 5-fluorouracil 600 mg/m(2), doxorubicin 60 mg/m(2), and cyclophosphamide 600 mg/m(2), every three weeks. All patients subsequently underwent modified radical mastectomy approximately two weeks after the last cycle of chemotherapy. Pathologic complete response rates were 25.5% and 10.2% in the study and the control group, respectively (P = 0.049). Similarly, clinical complete response rates were 27.6% and 10.2% in the study and the control group, respectively (P = 0.037). In the subgroup analysis of hormone receptor-positive cases, the complete response rates were more prominent in study group compared with control group. Common treatment-related side effects such as nausea, vomiting, bone marrow suppression, and mucositis were similar in both groups, but hot flush was more prevalent in study group compared with control group (P = 0.023). The addition of letrozole concurrently with neoadjuvant chemotherapy provides a higher clinical and pathologic response rates with acceptable toxicity compared with chemotherapy alone in postmenopausal women with locally advanced sensitive breast cancer.     

Role of neoadjuvant therapy in the management of pancreatic cancer: is the era of biomarker-directed therapy here?

Pancreatic cancer is the 4th leading cause of cancer-related death. Complete surgical resection (CR0) is considered the only curative treatment. Most patients present with unresectable or borderline resectable disease. Many small phase i/ii trials have tried to address the role of neoadjuvant treatment using chemotherapy with or without chemoradiation in the management of locally advanced disease. However, many of them looked at the rate of CR0 resection and the feasibility of such treatment. A trend for improved overall survival has been observed in the group of patients with borderline resectable disease who completed neoadjuvant treatment. A large proportion of patients progress while on treatment, sparing them from unnecessary surgery.We searched the PubMed database (using the key words “pancreatic cancer,” or “pancreatic neoplasm,” or “pancreatic adenocarcinoma,” and “neoadjuvant treatment,” or “neoadjuvant chemotherapy,” or “neoadjuvant radiation therapy,” or “neoadjuvant chemo-radiation,” or “adjuvant therapy” [all fields] and “clinical trial” or “study”) and abstracts presented at the American Society of Clinical Oncology meetings on gastrointestinal cancers. Here, we review the most recent papers that present results on neoadjuvant therapy in pancreatic cancer. All but one report used overall survival as an endpoint. Unfortunately, there are no valid biomarkers predicting tumour progression or recurrence, and response to treatment than can help to guide therapeutic choices.Our recommendation is to consider neoadjuvant treatment in cases of borderline resectable disease. In patients with primary resectable tumours, surgery followed by adjuvant treatment and enrollment on adjuvant treatment studies would be appropriate.     

What is the predictor for invasion in non-palpable breast cancer with microcalcifications?

PURPOSE: To assess the presence of invasion in non-palpable breast cancer with microcalcifications. MATERIAL AND METHODS: We investigated 157 patients with non-palpable breast cancer with microcalcifications, who had undergone stereotactic core biopsy or vacuum-assisted breast biopsy and operation at the Cancer Institute Hospital between 1995 and 2001. We investigated the correlation between the area of calcification (maximum range of microcalcifications measured in mm by direct mammography), morphology of calcification on mammography, histological subtype of intraductal carcinoma (comedo or non-comedo) and frequency of invasion, and lymph node metastasis. The chi-square test was used in the statistical analysis and p values less than 0.05 were considered statistically significant. RESULTS: Invasion was observed in 33 of 157 pts (21%), of whom 23 showed minimal invasion, which is less than 0.5 cm in greatest diameter. The risk of invasion was 13% within 10 mm of the microcalcifications (n =70), 25% from 11 to 30 mm (n =59), and 32% more than 31 mm from the microcalcifications (n =28). The risk of invasion was 16% for punctate-round and amorphous type (n =87) microcalcifications, and 27% for pleomorphic and linear-branching types (n =70)(p =0.092). In addition, invasion was found 10% of the time within 10 mm of punctate-round and amorphous type microcalcifications, and 20% of the time at 11 mm or more. On the other hand, invasion was found 15% of the time within 10 mm of pleomorphic and linear-branching type microcalcifications, and 37% of the time at 11 mm or more. In 72 cases of intraductal carcinoma diagnosed by pathological examination, invasion was found in 10 of 31 (32%) comedo type intraductal carcinomas and in 5 of 41 (12%) non-comedo types (p =0.0379). There were 5 cases (3.2%) with axillary lymph node metastasis, all of which widely extended more than 21 mm from the microcalcifications. CONCLUSION: The risk of invasion was 10% within 10 mm of punctate-round and amorphous type microcalcifications, and 37% at more than 11 mm of pleomorphic, linear-branching microcalcifications.     

What constitutes high-risk locally advanced prostate cancer?

Excluding basal and squamous cell cancers of the skin, prostate cancer is the most common malignancy diagnosed in the United States. With increasing awareness and routine prostate-specific antigen testing, a remarkable migration in the clinical presentation of the disease has occurred in the past 20 years. An increasingly greater proportion of men are diagnosed with clinically organ-confined disease. In parallel, the incidence of men presenting with clinically bulky locoregional or metastatic disease has decreased. Despite the stage migration, when clinical and pathologic parameters are taken into account, a significant number of men with clinically localized prostate cancer do not have truly organ-confined disease. Such men might not to be cured with single modality, locally directed therapies. Thus, prostate cancer represents a disease spectrum with a number of biologic and clinical factors determining disease extent. An overview of some of these aspects of the disease is presented.     

Treatment of locally advanced prostate cancer: is chemotherapy the next step?

PURPOSE: Management of locally advanced prostate cancer remains controversial. Various single and combination modality approaches have been advocated, but an accepted standard of care remains undefined. The purpose of this review is to define the current knowledge in managing locally advanced prostate cancer and to propose new treatment approaches based on current knowledge. MATERIALS AND METHODS: A MEDLINE search to detect all relevant articles on the management of locally advanced prostate cancer was performed. A review of the staging, natural history, and prognosis of this disease was also performed. RESULTS: The lack of a clearly defined treatment approach to patients with locally advanced prostate cancer stems from multiple factors, including ambiguities in clinical staging, inadequate knowledge of the natural history of the cancer, and a dearth of comparative randomized trials evaluating efficacy of different therapies. Single modality treatment, including radical prostatectomy (RP) or external-beam radiotherapy alone, is associated with high rates of failure. The use of adjuvant hormonal ablation therapy in combination with external-beam radiotherapy has shown improvement in progression-free and overall survival, although similar improvements have not been clearly demonstrated for surgical patients treated with hormonal therapy. New advances in chemotherapy for hormone-refractory prostate cancer suggest that response rates may be as high as 50% or more, and current trials are evaluating the addition of chemotherapy to hormonal ablation in either surgery or radiation therapy in locally advanced prostate cancer. CONCLUSION: Optimal management of locally advanced prostate cancer remains undefined. Standard treatment options include RP, external-beam radiotherapy, or hormonal ablation therapy, alone or in combination. New approaches being tested include improved methods for delivering radiation or combining hormonal ablation with surgery or radiation. It is possible that other forms of systemic therapy, including chemotherapy, may become important components of multimodality treatment. Clinical trials designed to test this hypothesis are ongoing.