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Molecular determinants of post-mastectomy breast cancer recurrence.

ABSTRACT: Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This included 32 LRR, 34 DM, and 49 controls. RNAseq was performed on primary tumors in 110 patients; with no difference in RNA profiles between patients with LRR, DM, or controls. DNA analysis on 57 primary tumors (17 LRR, 15 DM, and 25 controls) identified significantly more NF1 mutations and mitogen-activated protein kinase (MAPK) pathway gene mutations in patients with LRR (24%, 47%) and DM (27%, 40%) compared to controls (0%, 0%; p < 0.0001 and p = 0.0070, respectively). Three patients had matched primary vs. LRR samples, one patient had a gain of a NF1 mutation in the LRR. There was no significant difference between the groups for PTEN loss or cleaved caspase 3 expression. The mean percentage Ki 67 labeling index was higher in patients with LRR (29.2%) and DM (26%) vs. controls (14%, p = 0.0045). In summary, mutations in the MAPK pathway, specifically NF1, were associated with both LRR and DM, suggesting that alterations in MAPK signaling are associated with a more aggressive tumor phenotype. Validation of these associations in tissues from randomized trials may support targeted therapy to reduce breast cancer recurrence.

SUBMITTER: Keene KS

PROVIDER: S-EPMC6185974 | biostudies-literature | 2018

REPOSITORIES: biostudies-literature

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Molecular determinants of post-mastectomy breast cancer recurrence.

Keene Kimberly S KS King Tari T Hwang E Shelley ES Peng Bo B McGuire Kandace P KP Tapia Coya C Zhang Hong H Bae Sejong S Nakhlis Faina F Klauber-Demore Nancy N Meszoely Ingrid I Sabel Michael S MS Willey Shawna C SC Eterovic Agda Karina AK Hudis Cliff C Wolff Antonio C AC De Los Santos Jennifer J Thompson Alastair A Mills Gordon B GB Meric-Bernstam Funda F

NPJ breast cancer 20181012

Breast cancer (BC) adjuvant therapy after mastectomy in the setting of 1-3 positive lymph nodes has been controversial. This retrospective Translational Breast Cancer Research Consortium study evaluated molecular aberrations in primary cancers associated with locoregional recurrence (LRR) or distant metastasis (DM) compared to non-recurrent controls. We identified 115 HER2 negative, therapy naïve, T 1-3 and N 0-1 BC patients treated with mastectomy but no post-mastectomy radiotherapy. This inclu ...[more]

PMID: 30345349

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Project description:PurposeThe goal of this study was to explore the perspectives and practice of radiation oncologists who treat breast cancer patients who have had breast reconstruction.MethodsIn 2010, an original electronic survey was sent to all physician members of the American Society of Radiation Oncology, National Cancer Research Institute-Breast Cancer Studies Group in the United Kingdom, Thai Society of Therapeutic Radiology and Oncology, Swiss Society of Radiation Oncology, and Turkish Radiation Oncology Society. We identified factors associated with radiation oncologists who treat breast cancer patients with reconstruction performed prior to radiation and obtained information regarding radiation management of the breast reconstruction.Results358 radiation oncologists responded, and 60% of the physicians were from the United States. While 64% of participants agree or strongly agree that breast image affects a woman's quality of life during radiation, 57% feel that reconstruction challenges their ability to deliver effective breast radiation. Compared with other countries, treatment within the United States was associated with a high reconstruction rate (>/= 50% of mastectomy patients) prior to radiation (p < 0.05). Delayed-immediate reconstruction with a temporary tissue expander was more common in the United States than in other countries (52% vs. 23%, p = 0.01). Among physicians who treat patients with tissue expanders, the majority (60%) prefer a moderately inflated implant with 150-250 cc of fluid rather than a completely deflated (13%) or inflated expander (28%) during radiation. Among radiation oncologists who treat reconstructions, 49% never use bolus and 40% never boost a breast reconstruction. United States physicians were more likely than physicians from other countries to boost or bolus the reconstruction irrespective of the type of reconstruction seen in their clinic patients (p < 0.01).ConclusionsGreat variation in practice is evident from our study of radiation treatment for breast cancer patients with reconstruction. Further research on the impact and delivery of radiation to a reconstructed breast may validate some of the observed practices, highlight the variability in treatment practice, and help create a treatment consensus.

Project description:BackgroundBreast cancer survivors may be at risk of experiencing rotator cuff disease after treatment. Biomechanical alterations following surgery potentially predispose survivors to develop this disorder.ObjectiveTo examine scapular kinematics in breast cancer survivors with and without impingement pain during an overhead reach task.DesignA cross-sectional study.MethodsThree surgery groups were included: non-cancer controls, mastectomy-only survivors and post-reconstruction survivors. Breast cancer survivor groups were also categorized by the presence of impingement pain. Scapular motion was tracked during an overhead reach task, performed separately by both arms. Maximum scapular internal rotation, upward rotation and tilt were calculated. Two-way analyses of variance with interactions (p < .05) were used to test the effects of group (control, mastectomy-only, reconstruction) and impingement pain (pain, no pain) on each variable within a (left/right) side.ResultsScapular kinematics varied with the group by pain interaction. On the right side, the mastectomy-pain group had reduced upward rotation, while the reconstruction-pain group had higher upward rotation (mastectomy-only: 22.9° vs. reconstruction: 31.2°). On the left side, the mastectomy-pain group had higher internal rotation, while the reconstruction-pain group had reduced internal rotation (mastectomy-only: 45.1° vs. reconstruction: 39.3°). However, time since surgery was longer in the mastectomy-pain group than reconstruction-pain group, suggesting there may be a temporal component to kinematic compensations.ConclusionsThere are kinematic alterations in breast cancer survivors that may promote future development of rotator cuff disease. Compensations may begin as protective and progress to more harmful alterations with time.KEY MESSAGESScapular kinematics varied with surgery and pain interaction: upward rotation was lower and internal rotation higher in mastectomy-pain group, while upward rotation was higher and internal rotation lower in reconstruction-pain group.Kinematics alterations may also be associated with time since surgery, as the mastectomy-pain group had longer time since surgery than the reconstruction-pain group.Kinematic alterations may transition from protective to harmful over time.In-depth analyses by reconstruction type are needed to determine surgery-specific effects on kinematics and their potential impact on the development of rotator cuff disease.

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Molecular determinants of post-mastectomy breast cancer recurrence.

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Molecular determinants of post-mastectomy breast cancer recurrence.

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