Tag: breast-cancer

The combination of BRAF600E mutation and TERT promotor mutations increases risk of recurrence and death in papillary thyroid cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Most patients with papillary thyroid cancer (PTC) have an excellent prognosis:
    • But predicting which patients do not do well has been an ongoing area of interest
  • Ideally, identifying those at higher risk of cancer recurrence:
    • Would potentially allow the more aggressive therapies to be utilized when appropriate for patients with high risk papillary thyroid cancer
  • A lot of work has identified molecular markers, which are mutations in cancer-related genes that can help in the diagnosis of thyroid cancer on thyroid biopsy specimens
  • Two specific molecular markers, BRAFv600E and TERT promotor mutations:
    • Have been associated with aggressive tumor behavior and worse outcomes in papillary thyroid cancer
  • The BRAFv600E mutation is quite common in papillary thyroid cancer:
    • So using this mutation alone to predict outcome has been challenging, though it has been associated with poor prognosis
  • The TERT promoter mutation alone was not shown to cause adverse outcomes in some previous studies, though other studies suggested it was associated with a more aggressive clinical picture
  • A study by Moon S et al. aimed to determine the prognosis of papillary thyroid cancer in patients with either of these mutations alone or in combination by a review of the current studies:
    • Moon S et al. Effects of coexistent BRAFV600E and TERT promoter mutations on poor clinical outcomes in papillary thyroid cancer: a meta-analysis
  • Summary of the Study:
    • A literature review was done to identify studies that included BRAFV600Eand TERT promoter mutations in thyroid cancer
    • A total of 13 studies were identified
    • Data was extracted and reviewed for clinical information to include the number of males and females, age at diagnosis, cancer stage, spread to lymph nodes, extrathyroidal extention, spread outside of the neck, cancer recurrence and death
    • A total of 4347 patients with papillary thyroid cancer were evaluated in the study and 283 patients had both BRAFv600E and TERT promoter mutations
    • A BRAFv600E mutation alone:
      • Was related to advanced age at time of diagnosis, advanced cancer stage, extrathyroidal extension of tumor, and spread to lymph nodes, compared with no mutation
    • A TERT promoter mutation alone:
      • Was associated with older age at diagnoses, spread to lymph node and spread outside of the neck
    • The combination of BRAFv600E and TERT promoter mutations together when compared with no mutations:
      • Was associated with older age at diagnosis, male gender, advanced cancer staging, extrathyroidal extension, spread to lymph node and spread outside of the neck
    • Overall, the combination of BRAF600E and TERT mutations:
      • Was associated with high recurrence rate when compared with no mutations
    • Further, it was noted that the combination of mutations also had a higher risk of death than no mutations or BRAFv600E alone, although few patients were in this group
  • What are the implications to this study:
    • This study shows that molecular marker analysis can be used to identify patients that have more aggressive thyroid cancer
    • The combination of BRAFv600E and TERT promotor mutations worsens the prognosis for papillary thyroid cancer
    • Additionally, a limited data set suggested higher risk of death with the combination of BRAF600E and TERT promoter mutations
    • As we improve our understanding of the molecular changes in thyroid cancer, we will improve our ability to identify patients that have a more aggressive thyroid cancer
    • Ultimately this knowledge will lead to improved treatment options
    • Future studies must aim to determine if identifying these mutations at the time of diagnosis can lead to improved outcomes for patients at higher risk
#Arrangoiz #ThyroidSurgeon

Immediate Surgery Can Improve Long-Term Outcomes in Older Breast Cancer Patients

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Immediate surgery can improve outcomes among women age 70 and older who have operable breast cancer and are not receiving radiotherapy:
  • Results of the meta-analysis showed that patients who had immediate surgery:
    • Had lower rates of local recurrence early on, when compared to patients who had delayed surgery:
      • With longer follow-up, patients who had undergone surgery immediately also had lower rates of distant recurrence and breast cancer death
  • The meta-analysis included data from three trials encompassing 1082 women with breast cancer who were at least 70 years of age and had a median of 5 years on study:
    • The trials were all designed to compare immediate surgery to deferral of surgery until after progression, in the absence of radiotherapy
  • Results showed that, among patients with node-negative disease:
    • The rate of local recurrence at 5 years was 14.4% in patients who received tamoxifen plus surgery and 45.4% in patients who received tamoxifen alone (rate ratio [RR], 0.25; 95% CI, 0.19-0.34; P <.00001).
  • Among patients with node-positive disease:
    • The rate of local recurrence at 5 years was 6.8% in those treated with tamoxifen plus surgery and 48.1% in patients receiving tamoxifen alone (RR, 0.18; 95% CI, 0.11-0.29; P <.00001)
  • Immediate surgery leads to a very great reduction in the rates of local recurrence, and the curves separate immediately:
    • So that benefit is seen immediately, irrespective of nodal status, with really quite large absolute differences at 5 years
  • The study also found lower rates of distant recurrence and breast cancer death among patients who received immediate surgery:
    • However, those benefits only became apparent with longer follow-up:
      • The rate of distant recurrence at 15 years was 37.0% in patients who received tamoxifen plus surgery and 51.3% in patients who received tamoxifen alone (RR, 0.72; 95% CI, 0.57-0.90; P =.003)
      • The rate of breast cancer death at 15 years was 34.2% in patients who received tamoxifen plus surgery and 48.9% in those who received tamoxifen alone (RR, 0.68; 95% CI, 0.54-0.86; P =.002).
  • References:

Occult Breast Cancer

Rodrigo Arrangoiz MS, MD, FACS, FSSO
  • Occult breast cancer:
    • Which manifests as axillary lymph node metastasis:
      • Without the evidence of a primary breast tumor on clinical examination or mammography
    • It accounts for 0.3% to 1.0% of all breast cancers
  • The American College of Radiology:
    • Recommends the use of MRI for occult breast cancer patients:
      • Who do not have evidence of a breast primary on traditional radiological examination (mammogram and ultrasound) and clinical examination
    • Level I evidence has shown MRI is significantly more sensitive in detecting a primary lesion than mammography or ultrasound:
      • Identifying a primary tumor in 72% of cases that were originally deemed occult
  • Patients with occult breast cancer who have abnormalities demonstrated on MRI should then undergo evaluation with:
    • Targeted ultrasound plus ultrasound-guided needle biopsy or MRI-guided needle biopsy and receive treatment according to the clinical stage of the breast cancer
  • Treatment recommendations for those with negative MRI results and occult breast cancer presenting as isolated axillary metastases:
    • Are based on nodal status and breast cancer subtype
  • Most patients with axillary metastasis from an unknown breast primary:
    • Are candidates for neoadjuvant therapy
  • A meta-analysis reported outcomes for occult breast cancer in patients undergoing axillary lymph node dissection (ALND) (with or without radiation therapy [RT]) versus mastectomy:
    • It included 7 international studies, with 241 patients presenting between 1973 and 2011
    • The mean follow up was 62 months
    • There was no difference in survival, locoregional recurrence rate, or distant metastatic rate between those occult breast cancer patients who underwent mastectomy versus those who underwent ALND + breast RT (without breast surgery)
    • Radiotherapy improves locoregional recurrence and possibly mortality rates of patients undergoing ALND
    • Based on this meta-analysis, combined ALND and RT is an acceptable approach
  • The current National Comprehensive Cancer Network guidelines:
    • Recommend that patients with negative MRI results should be treated with mastectomy plus axillary lymph node dissection (modified radical mastectomy) OR ALND plus whole-breast irradiation
  • Approximately 40% of patients undergoing neoadjuvant chemotherapy for clinically node-positive disease:
    • Are successfully down staged in the axilla, and may be able to avoid ALND
    • Although this may prove to be safe for patients with primary occult breast cancer, there are no studies that have specifically addressed the safety of sentinel lymph node biopsy with targeted axillary dissection in this highly select subset
  • Treatment gold standard for occult breast cancer presenting with axillary metastases which remain clinically positive after neoadjvuant chemotherapy, remains ALND
  • References
    1. Ge L-P, Liu X-Y, Xiao Y, et al. Clinicopathological characteristics and treatment outcomes of occult breast cancer: a SEER population-based study. Cancer Manag Res. 2018;10:4381-4391. doi: 10.2147/CMAR.S169019
    2. Ofri A, Moore K. Occult breast cancer: where are we at? Breast. 2020;54:211-215. doi: 10.1016/j.breast.2020.10.012
    3. American College of Radiology. ACR practice parameter for the performance of contrast-enhanced magnetic resonance imaging (MRI) of the breast. Accessed April 7, 2023. https://www.acr.org/-/media/ACR/Files/Practice-Parameters/MR-Contrast-Breast.pdf?la1⁄4en.
    4. de Bresser J, de Vos B, van der Ent F, Hulsewé K. Breast MRI in clinically and mammographically occult breast cancer presenting with an axillary metastasis: a systematic review. Eur J Surg Oncol. 2010;36(2):114-119. doi: 10.1016/j.ejso.2009.09.007
    5. Macedo FIB, Eid JJ, Flynn J, Jacobs MJ, Mittal VK. Optimal surgical management for occult breast carcinoma: a meta-analysis. Ann Surg Oncol. 2016;23(6):1838-1844. doi: 10.1245/s10434-016-5104-8
    6. National Comprehensive Cancer Network. Breast Cancer. Version: 3.2023. Accessed April 7, 2023. https://www.nccn.org/professionals/physician_gls/pdf/breast.pdf
    7. American Society of Breast Surgeons. Consensus Statement on Axillary Management for Patients With In-Situ and Invasive Breast Cancer: a concise overview. Accessed April 17, 2023. https://www.breastsurgeons.org/docs/statements/management-of-the-axilla.pdf