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Should triple negative breast cancer (tnbc) subtype

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Should triple negative breast cancer (tnbc) subtype

  1. 1. SHOULD TRIPLE-NEGATIVE BREAST CANCER (TNBC) SUBTYPE AFFECT LOCAL- REGIONAL THERAPY DECISION MAKING?
  2. 2. The answer is YES
  3. 3. What is Triple Negative Breast cancer? ER , PR negative HER 2 neu negative Aggressive pathologic features a higher histology grade and mitotic index No hormonal treatment NO Trastuzumab Higher rate of &early recurrence distant metastasis to brain and lungs
  4. 4. Is There Hope ???!!!!!!!!!!!!!! Understanding the biology Basal-like 1 (BL-1) Basal-like 2 (BL-2) Immunomodulatory (IM) Mesenchymal (M) Mesenchymal stem-like (MSL) Luminal androgen receptor (LAR) Triple Negative Breast Cancer EGFR & CK5/6 (Positive) EGFR & CK5/6 (Negative)
  5. 5. Female patient 32 ys old , presented with mass in left breast (2*3) cm , tru cut biopsy was taken revealed , infiltrating duct carcinoma , ER , PR ,HER2 neu negative ( Triple Negative) . The patient has come to your office to discuss her treatment options , she talked to you about her chance for breast conserving surgery . What will be your advice????????? *In order to determine whether surgical choice has an impact on locoregional recurrence in patients with TNBC, several studies have investigated outcomes following treatments in TNBC compared with the general breast cancer population. *The aggressive nature of the TNBC subtype may appear to exclude such patients from treatment with breast-conservation therapy (BCT)
  6. 6. Parker et al* addressed this by carrying out a retrospective analysis of patients with TNBC, comparing their outcomes based on the surgical approach (BCT versus mastectomy). In this study, out of a total of 220 patients with TNBC, 61 (30%) patients underwent BCT and 141 (70%) patients underwent mastectomy. To determine whether the type of operative therapy had an impact on the outcome for patients with TNBC, overall survival (OS) and disease-free survival (DFS) were compared. The 5-year DFS rates for the BCT and mastectomy groups were 68% and 57%, respectively (P = 0.14). The 5-year OS was better for the BCT than for the mastectomy group (89% versus 69%; P = 0.018). Parker et al. concluded that selected patients with TNBC should be given the opportunity to benefit from the less aggressive BCT. *Parker CC, Ampil F, Burton G et al. Is breast conservation therapy a viable option for patients with triple-receptor negative breast cancer? Surgery 2010; 148.
  7. 7. Solin et al.* conducted a study of 519 women with breast cancer, 90 with TNBC. After BCT with radiation, women with TNBC showed a higher 8-year rate of any locoregional recurrence (8% versus 4%; P = 0.041) and a lower 8-year rate of freedom from distant metastases (81% versus 92%; P = 0.0066). Although women with TNBC had a higher rate of locoregional recurrence after breast reconstruction with RT, Following multivariate analysis, this difference was not statistically significant. *Solin LJ, Hwang WT, Vapiwala N. Outcome after breast conservation treatment with radiation for women with triple- negative early-stage invasive breast carcinoma. Clin Breast Cancer 2009; 9: 96–100.
  8. 8. Voduc et al classified patients into six subtypes, which included distinction of basal-like (ER/PR/HER2 negative, EFGR positive or CK5/6 positive) and TNBC-phenotype (ER/PR/HER2 negative, EGFR negative and CK5/6 negative) for analysis of LRR outcomes. LRR was highest among basal-like, but not nonbasal TNBC, and these LRR patterns were also similarly high when the two subtypes underwent BCT. These findings have also been*confirmed in recent meta-analyses Abdulkarim et al analyzed LRR outcomes of T1–2, N0 TNBC treated with BCT compared with modified radical mastectomy and reported an absolute reduction of LRR risk by 6% in their BCT cohort.** **Abdulkarim BS, Cuartero J, Hanson J, et al. Increased risk of locoregional recurrence for women with T1-2N0 triple- negative breast cancer treated with modified radical mastectomy without adjuvant radiation therapy compared with breast-conserving therapy. J Clin Oncol. 2011;29:2852-2858. *Wang J, Xie X, Wang X, et al. Locoregional and distant recurrences after breast conserving therapy in patients with triple-negative breast cancer: a meta-analysis. Surg Oncol. 2013;22:247-255
  9. 9. So, your patient has gone for breast conserving surgery with lumpectomy with negative margin and adequate axillary evacuation with pathological staging (pT2N0M0) then she has returned to you for further management . Here is the question , Does being triple negative will impact your descion about her adjuvant radiotherapy???? *Adjuvant radiotherapy is a key component in BCS *Given the ongoing excitement generated by newer radiation delivery methods that deliver shorter courses of radiation for early-stage breast cancer. *APBI delivers radiation to a small area surrounding the lumpectomy cavity (and not all breast tissue) using a variety of delivery methods, reducing treatment from five to six and a half weeks with conventionally fractionated whole- breast radiation to less than five days with APBI, thus, lower treatment costs, increasing patient convenience, and potentially decreasing toxicity with smaller radiated volumes. BUT, patterns of recurrence after BCT by subtype suggest more true recurrences (around the tumor bed) for TNBC
  10. 10. Although there is a paucity of data on outcomes by subtype from prospective APBI trials, one recent prospective APBI study found an unacceptably high five-year actuarial in-breast failure rate of 33% in their TNBC subset * *Sioshansi S, Ehdaivand S, Cramer C, et al. Triple negative breast cancer is associated with an increased risk of residual invasive carcinoma after lumpectomy. Cancer. 2012;118:3893-3898
  11. 11. The rising question here , if this patient had done MRM , is there will be an indication for adjuvant radiotherapy??? Abdulkarim et al. compared the locoregional recurrence risk following MRM without adjuvant RT with BCS in a population of patients with TNBC and a subgroup of patients with T1-2N0 TNBC. At a median follow-up of 7.2 years, %10 of patients with TNBC developed locoregional recurrence, and MRM without RT represented the only independent prognostic factor associated with increased risk of locoregional recurrence in the T1-2N0 subgroup when compared with BCS Other studies have also suggested that some T1-2N0 patients may benefit from MRM plus adjuvant RT , which is not recommended in the current guidelines.
  12. 12. There is a study found a decreased effect of PMRT for patients with TNBC when compared with other breast cancer subtypes (ER- positive/PR-positive and the ER-positive/PR-positive/HER2- negative subtype). Taken together, the authors suggested relative radioresistance of the TNBC subtype as a consequence of the ER-negative receptor status. ER expression results in a decrease in cell-cycle duration, reducing the time available for the repair of DNA damage caused by radiation. It was suggested that ER-negative cells as found in TNBC and basal-like breast cancer would thus exhibit radioresistance, as DNA repair is allowed to progress during the slower cell cycle.
  13. 13. Do you think that genetic testing for this patient will make a sense in decision making for locoregional management?? *There is some notable overlap between the morphologic and phenotypic features of breast cancer in BRCA1 carriers and sporadic TNBC. These strong resemblances suggest a commonality in one or more defects in the functions of the BRCA1 pathway for both BRCA1-associated and sporadic TNBC. *Although much remains to be learned about the clinical implications regarding the resemblances between BRCA1- associated and sporadic TNBC, knowledge of germline BRCA mutation status is an important component of local-regional management decisions.
  14. 14. It is essential to recognize that the increased lifetime risk of ipsilateral breast relapse and contralateral breast cancer after BCT in BRCA carriers is not shared by sporadic TNBC. Thus, all patients with TNBC should undergo risk assessment for genetic susceptibility *Though mutation status alone should not direct local-regional management, it guides recommendations for additional risk-reducing surgical interventions, such as oophorectomy or contralateral prophylactic mastectomy, which may be performed simultaneously with definitive surgery. *The presence of a BRCA mutation should not preclude BCT in patients who are otherwise appropriate candidates, as the data suggest that BC-specific survival and overall survival for hereditary breast cancer is independent of local treatment choice.
  15. 15. Given the high long-term risks of new in-breast and contralateral breast primaries, definitive mastectomy with simultaneous contralateral prophylactic mastectomy is the local-regional management pathway that is most commonly selected by patients with hereditary breast cancer
  16. 16. Triple negative breast cancer represent a major obstacle regarding its aggressiveness and lack of targets to be targated . TNBC is not contraindication for breast conserving surgery. Following breast conservation , conventional radiotherapy with boost is recommended Genetic risk assessment for TNBC is recommended
  17. 17. Searching for targets is the most important rising hope in management of triple negative breast cancer

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