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G Bruce Mann

Publications and source records attributed to G Bruce Mann.

8 recordsLinked to original sources

Neoadjuvant palbociclib in women with operable, hormone receptor-positive breast cancer.

The addition of a cyclin-dependent kinase 4/6 (CDK4/6) inhibitor to endocrine therapy augments biological response in breast cancer. This phase III randomized, double-blind study evaluated the efficacy of adding palbociclib to neoadjuvant endocrine therapy (NET) for operable, hormone receptor-positive human epidermal growth factor receptor 2 (HER2)-negative breast cancer. Patients randomly received 16 weeks of endocrine therapy (letrozole for postmenopausal and tamoxifen plus ovarian function suppression for pre-/perimenopausal patients) plus palbociclib or placebo. The co-primary endpoints included preoperative endocrine prognostic index (PEPI) score and EndoPredict (EPclin) risk score according to the gatekeeping procedure. Of 141 randomized patients, 130 completed the treatment with surgical samples evaluable for endpoints in 126 patients. The proportion of patients with a low, moderate, and high PEPI score was 15.2, 50.0, and 34.8% in the palbociclib arm and 13.3, 55.0, and 31.7% in the placebo arm, respectively, with no statistical difference (one-sided P = 0.563). Statistical analysis was not performed on EPclin risk score. No new safety signals were reported. Permanent treatment discontinuation by adverse events was reported for seven (9.7%) and zero patients in the palbociclib and placebo arms, respectively. In conclusion, the addition of palbociclib to NET did not improve the efficacy. ClinicalTrials.gov NCT03969121.

Humans↗

Adjuvant therapy in gastric cancer.

Gastric cancer has a poor prognosis. The majority of patients will relapse after definitive surgery, and 5-year survival after surgery remains poor. The role of adjuvant therapy in gastric cancer has been controversial given the lack of significant survival benefit in many randomized studies so far. The results of a large North American study (Gastrointestinal Cancer Intergroup Trial INT 0116) reported that postoperative chemoradiotherapy conferred a survival advantage compared with surgery alone, which has led to the regimen being adopted as a new standard of care. However, controversies still remain regarding surgical technique, the place of more effective and less toxic chemotherapy regimens, and the use of more modern radiation planning techniques to improve treatment delivery and outcome in the adjuvant and neoadjuvant setting. This article reviews the current status of the adjuvant treatment for gastric cancer including discussion on the research directions aimed at optimizing treatment efficacy. Issues such as the identification of patients who are more likely to benefit from adjuvant therapy are also addressed. Further clinical trials are needed to move towards better consensus and standardization of care.

Chemotherapy, Adjuvant↗

Reliance on hormone receptor assays of surgical specimens may compromise outcome in patients with breast cancer.

PURPOSE: To assess the concordance of breast cancer immunohistochemical receptor assays on core biopsy and surgical specimens. PATIENTS AND METHODS: We identified 100 patients whose core biopsy and definitive surgical specimens were processed in our hospital. New sections, with core and surgical specimens on the same slides, were stained for estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER-2) immunohistochemistry (IHC). Two pathologists assessed the sections independently. Raw scores and clinically significant groupings were compared. RESULTS: Concordance for ER, PR, overall hormone receptor (HR), and HER-2 status was seen in 86%, 83%, 90%, and 80% of patients, respectively. The core was positive, while the surgical specimen was negative in 13%, 11%, 9%, and 1% of patients, respectively. Using a log-linear model, differences in ER, PR, and HER-2 staining were all in the direction of stronger staining in the cores, and were statistically significant. Nine percent (95% CI, 4.2% to 16.4%) of women in this group would have had endocrine therapy inappropriately withheld if management decisions were based on surgical specimen results alone. CONCLUSION: ER and PR assays on core biopsy specimens are more reliable than assays on surgical specimens. Receptor IHC should be performed on core biopsy specimens to avoid patients with HR positive cancers not receiving appropriate hormonal therapy and being overtreated with systemic chemotherapy. Biopsy should be considered in patients with "receptor negative" cancer and recurrent disease.

Adult↗

Comparison of blue dye and isotope with blue dye alone in breast sentinel node biopsy.

BACKGROUND: Sentinel lymph node biopsy (SNB) is rapidly gaining acceptance as an alternative to axillary dissection (AD) in patients with early breast cancer. Debate continues regarding the optimum technique for sentinel node (SN) mapping. We have used our series of 364 SNBs to compare two different techniques. METHODS: A retrospective review of patients undergoing SNB by surgeons in our breast service. Overall results were analysed, with particular attention to those having blue dye alone and those having blue dye in combination with radio-labelled colloid. SNs were analysed using haematoxylin-eosin and immunohistochemical staining. RESULTS: SN identification rates were similar: 96% for dye alone and 89% for dye and colloid in combination. Twenty-one per cent of SN mapped with dye alone contained metastases, compared to 30% with dye and colloid in combination. The false-negative rate was correspondingly higher in the dye alone group (21 vs 2.8%). CONCLUSION: SNB using dye and colloid in combination was significantly superior to dye alone in this series. We advocate using both dye and colloid for intraoperative SN mapping.

Adult↗

Molecular detection of micrometastatic breast cancer in histopathology-negative axillary lymph nodes correlates with traditional predictors of prognosis: an interim analysis of a prospective multi-institutional cohort study.

OBJECTIVE: We sought to establish the clinical relevance of micrometastatic disease detected by reverse transcription polymerase chain reaction (RT-PCR) in axillary lymph nodes (ALN) of breast cancer patients. BACKGROUND: The presence of ALN metastases remains one of the most valuable prognostic indicators in women with breast cancer. However, the clinical relevance of molecular detection of micrometastatic breast cancer in sentinel lymph nodes (SLN) and nonsentinel ALN has not been established. METHODS: Four hundred eighty-nine patients with T1-T3 primary breast cancers were analyzed in a prospective, multi-institutional cohort study. ALN were analyzed by standard histopathology (H&E staining) and by multimarker, real-time RT-PCR analysis (mam, mamB, muc1, CEA, PSE, CK19, and PIP) designed to detect breast cancer micrometastases. RESULTS: A positive marker signal was observed in 126 (87%) of 145 subjects with pathology-positive ALN, and in 112 (33%) of 344 subjects with pathology-negative ALN. In subjects with pathology-negative ALN, a positive marker signal was significantly associated with traditional indicators of prognosis, such as histologic grade (P = 0.0255) and St. Gallen risk category (P = 0.022). Mammaglobin was the most informative marker in the panel. CONCLUSION: This is the first report to show that overexpression of breast cancer-associated genes in breast cancer subjects with pathology-negative ALN correlates with traditional indicators of disease prognosis. These interim results provide strong evidence that molecular markers could serve as valid surrogates for the detection of occult micrometastases in ALN. Correlation of real-time RT-PCR analyses with disease-free survival in this patient cohort will help to define the clinical relevance of micrometastatic disease in this patient population.

Adult↗

Gastric cancer.

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Humans↗

Alternative sites of injection for sentinel lymph node biopsy in breast cancer.

BACKGROUND: Sentinel node biopsy is rapidly gaining popularity as a less invasive approach to nodal staging in breast cancer. The optimal route of injection of radiocolloids and dye is controversial. The purpose of the present paper was to review and assess the literature. METHODS: A MEDLINE search for reports of studies involving different injection sites of colloid and/or dye was performed. RESULTS: Although controversial, current evidence suggests that subareolar (SA) or intradermal/subdermal (ID/SD) injection will map the same axillary sentinel nodes (SN) as peritumoral (PT) injection in the vast majority of cases, is at least as successful, and is better logistically. Peritumoral, but not alternative routes, identify extra-axillary sentinel nodes, which are important in a minority of patients. CONCLUSIONS: It is recommended that at least some of the radiocolloid be injected peritumorally to avoid missing those SN not located in the ipsilateral axilla. Injection of the dye and a portion of radiocolloid in an ID/SA location is reasonable to take advantage of the general ease and accuracy of ID/SA injections in identifying axillary SN.

Breast↗