Dataset Information

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

ABSTRACT:

Purpose

Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases.

Results

Transcriptomic analyses identified CDKN2A/p16 as a gene potentially associated with brain metastases.

Materials and methods

Fifty-two patients with HER2-overexpressing or triple-negative breast carcinoma with lymph nodes and distant metastases were included in this study. Transcriptomic analyses were performed on laser-microdissected tumor cells from 28 metastatic lymph-nodes. Supervised analyses compared the transcriptomic profiles of women who developed brain metastases and those who did not. As a validation series, we studied metastatic lymph-nodes from 24 other patients.Immunohistochemistry investigations showed that p16 mean scores were significantly higher in patients with brain metastases than in patients without (7.4 vs. 1.7 respectively, p < 0.01). This result was confirmed on the validation series. Multivariate analyses showed that the p16 score was the only variable positively associated with the risk of brain metastases (p = 0.01).With the same threshold of 5 for p16 scores using a Cox model, overall survival was shorter in women with a p16 score over 5 in both series.

Conclusions

The risk of brain metastases in women with HER2-overexpressing or triple-negative breast cancer could be better assessed by studying p16 protein expression on surgically removed axillary lymph-nodes.

SUBMITTER: Furet E

PROVIDER: S-EPMC5514912 | biostudies-literature | 2017 Jun

REPOSITORIES: biostudies-literature

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Publications

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

Furet Elise E El Bouchtaoui Morad M Feugeas Jean-Paul JP Miquel Catherine C Leboeuf Christophe C Beytout Clémentine C Bertheau Philippe P Le Rhun Emilie E Bonneterre Jacques J Janin Anne A Bousquet Guilhem G

Oncotarget 20170601 23

<h4>Purpose</h4>Metastatic breast cancer is a leading cause of mortality in women, partly on account of brain metastases. However, the mechanisms by which cancer cells cross the blood-brain barrier remain undeciphered. Most molecular studies predicting metastatic risk have been performed on primary breast cancer samples. Here we studied metastatic lymph-nodes from patients with breast cancers to identify markers associated with the occurrence of brain metastases.<h4>Results</h4>Transcriptomic an ...[more]

PMID: 28445153

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Project description:ContextImmunochemical staining of sentinel lymph nodes (SLNs) and bone marrow identifies breast cancer metastases not seen with routine pathological or clinical examination.ObjectiveTo determine the association between survival and metastases detected by immunochemical staining of SLNs and bone marrow specimens from patients with early-stage breast cancer.Design, setting, and patientsFrom May 1999 to May 2003, 126 sites in the American College of Surgeons Oncology Group Z0010 trial enrolled women with clinical T1 to T2N0M0 invasive breast carcinoma in a prospective observational study.InterventionsAll 5210 patients underwent breast-conserving surgery and SLN dissection. Bone marrow aspiration at the time of operation was initially optional and subsequently mandatory (March 2001). Sentinel lymph node specimens (hematoxylin-eosin negative) and bone marrow specimens were sent to a central laboratory for immunochemical staining; treating clinicians were blinded to results.Main outcome measuresOverall survival (primary end point) and disease-free survival (a secondary end point).ResultsOf 5119 SLN specimens (98.3%), 3904 (76.3%) were tumor-negative by hematoxylin-eosin staining. Of 3326 SLN specimens examined by immunohistochemistry, 349 (10.5%) were positive for tumor. Of 3413 bone marrow specimens examined by immunocytochemistry, 104 (3.0%) were positive for tumors. At a median follow-up of 6.3 years (through April 2010), 435 patients had died and 376 had disease recurrence. Immunohistochemical evidence of SLN metastases was not significantly associated with overall survival (5-year rates: 95.7%; 95% confidence interval [CI], 95.0%-96.5% for immunohistochemical negative and 95.1%; 95% CI, 92.7%-97.5% for immunohistochemical positive disease; P = .64; unadjusted hazard ratio [HR], 0.90; 95% CI, 0.59-1.39; P = .64). Bone marrow metastases were associated with decreased overall survival (unadjusted HR for mortality, 1.94; 95% CI, 1.02-3.67; P = .04), but neither immunohistochemical evidence of tumor in SLNs (adjusted HR, 0.88; 95% CI, 0.45-1.71; P = .70) nor immunocytochemical evidence of tumor in bone marrow (adjusted HR, 1.83; 95% CI, 0.79-4.26; P = .15) was statistically significant on multivariable analysis.ConclusionAmong women receiving breast-conserving therapy and SLN dissection, immunohistochemical evidence of SLN metastasis was not associated with overall survival over a median of 6.3 years, whereas occult bone marrow metastasis, although rare, was associated with decreased survival.Trial registrationclinicaltrials.gov Identifier: NCT00003854.

Project description:ImportanceThe need for completion thyroidectomy in patients with incidental metastatic lymph nodes after partial thyroidectomy is unclear.ObjectiveTo investigate the outcomes of patients with incidental metastatic lymph nodes following partial thyroidectomy.Design, setting, and participantsA retrospective review of a prospectively maintained thyroid cancer database from 1985 to 2015 was carried out at a head and neck surgery practice at a tertiary referral cancer center. A total of 74 patients who underwent thyroid lobectomy or thyroid isthmusectomy between 1985 and 2015 and were found to have incidental metastatic lymph nodes on final pathologic analysis and were selected to be observed without immediate completion thyroidectomy were included. A separate group of additional 11 patients who underwent immediate completion thyroidectomy was also identified and reviewed.Main outcome and measureAnalysis took place from February to May 2022. Recurrence-free survival outcomes of patients found to have incidental metastatic lymph nodes on final pathologic analysis following partial thyroidectomy with no immediate completion thyroidectomy.ResultsA total of 74 patients were observed, with a median (IQR) age of 39 (28-49) years; 44 (59%) were women. Sixty-four patients underwent thyroid lobectomy and 10 patients had isthmusectomy. Classic papillary thyroid carcinoma was the most common histologic type (34 [46%]). Vascular invasion and microscopic extrathyroidal extension were present in 11 patients (16%) and 22 patients (30%), respectively. Positive margins were identified in 5 patients (7.8%). Size of metastatic lymph nodes ranged between 0.07 cm and 1.2 cm. No extranodal extension was reported. A total of 52 patients (70%) were classified as intermediate risk for recurrence based on the American Thyroid Association risk stratification system. The median (IQR) follow up was 48.15 (15.4-86.1) months, during which only 1 patient had a regional recurrence. Another patient underwent delayed completion thyroidectomy for a contralateral lobe malignant abnormality. Recurrence-free survival, disease-specific survival, and overall survival were 97.4%, 100%, and 96.2%, respectively. A separate group of 11 patients who underwent immediate completion thyroidectomy were reviewed. These patients were more likely to have tall-cell papillary thyroid carcinoma (6 [55%] vs 13 [18%]), multifocality (9 [82%] vs 28 [41%]), microscopic extrathyroidal extension (8 [73%] vs 22 [30%]), and positive margins (3 [30%] vs 5 [7.8%]) compared with patients who were under observation only.Conclusion and relevanceCompletion thyroidectomy may not be necessary in appropriately selected patients who are found to have incidental metastatic lymph nodes (N1a) after partial thyroidectomy for localized well-differentiated thyroid cancer.

Project description:BackgroundIndividualized decisions are required in early-stage breast cancer patients. We aimed to establish a novel model for predicting non-sentinel lymph node (SLN) metastases in patients with positive SLNs, using preoperative and intraoperative characteristics and inflammatory indicators.MethodsThe data of 489 patients with invasive breast cancer were retrospectively collected from Xuanwu Hospital between 2014 and 2021. Among them, 96 patients with at least one positive SLN were used to build the predictive model. Univariate and multivariate analyses were performed to identify the risk factors of non-SLN metastases. A nomogram was developed using these risk factors and was validated by calibration curves. The area under the receiver operating characteristics curve (AUC) and decision curve analyses (DCA) were used to compare our novel nomogram with the Memorial Sloan Kettering Cancer Center (MSKCC) nomogram. Cross-validation was performed for further internal validation of the predictive model. External validation was conducted using another treatment group (n=46 patients) in Xuanwu Hospital.ResultsNon-SLN metastases occurred in 42 of the 83 patients with positive SLNs (50.6%). Multivariate stepwise logistic regression indicated that the risk factors were age (P=0.032), number of positive SLNs (P=0.020), number of negative SLNs (P=0.011), resected tumor size (P=0.038), and monocyte count (P=0.012). A predictive model was developed and virtualized by nomogram using these five risk factors. The AUC of our nomogram was 0.867, which was significantly higher than that of the MSKCC model. DCA also showed a superior clinical value for our novel nomogram. After 10-fold cross-validation with 400 times repetitions, the AUC of our model was still 0.830. External validation of our model showed an AUC of 0.727. The model was well-calibrated in the internal and external validation series.ConclusionsA five-factor nomogram was developed for predicting non-SLN metastases in early-stage breast cancer patients. This novel tool exhibited good accuracy and could assist clinicians with intraoperative decisions in breast cancer patients with positive SLNs.

Dataset Information

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

Purpose

Results

Materials and methods

Conclusions

Publications

Increased risk of brain metastases in women with breast cancer and p16 expression in metastatic lymph-nodes.

Similar Datasets

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