Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• Trastuzumab and pertuzumab can cause:
  • Decrease in ejection fraction in up to 20% of patients:
    • Although this is often reversible
• Trastuzumab:
  • Can less commonly cause pneumonitis
• Pertuzumab:
  • Can cause rash and diarrhea

• References:
  • Gianni L, Pienkowski T, Im YH, Roman L, Tseng LM, Liu MC, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32.
  • Schneeweiss A, Chia S, Hickish T, Harvey V, Eniu A, Hegg R, et al. Pertuzumab plus trastuzumab in combination with standard neoadjuvant anthracycline-containing and anthracycline-free chemotherapy regimens in patients with HER2-positive early breast cancer: a randomized phase II cardiac safety study (TRYPHAENA). Ann Oncol. 2013;24(9):2278-2284.

#Arrangoiz #CancerSurgeon #BreastSurgeon #CASO #CenterforAdvancedSurgicalOncology #BreastCancer

What is the preferred adjuvant regimen for an invasive ductal carcinoma, ER positive, PR positive, HER2 positive by immunohistochemistry for a 0.9 cm grade tumor with 0/2 sentinel lymph nodes involved with tumor?

• The APT trial:
  • Showed a 3-year survival free rate from invasive disease of 98.7% for node negative tumors up to 3 cm in size:
    • With use of weekly paclitaxel / trastuzumab

• References:
  • Tolaney SM, Barry WT, Dang CT, Yardley DA, Moy B, Marcom PK, et al. Adjuvant paclitaxel and trastuzumab for node-negative, HER2-positive breast cancer. New Engl J Med. 2015;372(2):134-141.
  • Tolaney SM, Guo H, Pernas S, Barry WT, Dillon DA, Ritterhouse L. Seven-year follow-up analysis of adjuvant paclitaxel and trastuzumab trial for node-negative, human epidermal growth factor receptor 2-positive breast cancer.J Clin Oncol. 2019;37(22):1868-1875.

#Arrangoiz #BreastSurgeon #CancerSurgeon #SurgicalOncology #CASO #CenterforAdvancedSurgicalOncology

• Neutropenia is found in up to 79.5% of patients on palbociclib:
  • Neutropenia and the risk for infections must be discussed with patients prior to initiation of treatment
• Other common adverse effects of this drug include:
  • Fatigue (37.4%)
  • Nausea (35.1%)
  • Alopecia (32.9%)

• References:
  • Finn RS, Martin M, Rugo HS, Jones S, Im SA, Gelmon K, et al. Palbociclib and Letrozole in advanced breast cancer. New Engl J Med. 2016;375(20):1925-1936.
  • Finn RS, Crown JP2, Lang I3, Boer K4, Bondarenko IM5, Kulyk SO, et al. The cyclin-dependent kinase 4/6 inhibitor palbociclib in combination with letrozole versus letrozole alone as first-line treatment of oestrogen receptor-positive, HER2-negative, advanced breast cancer (PALOMA-1/TRIO-18): a randomised phase 2 study. Lancet Oncol. 2015;16(1):25-35.

#Arrangoiz #BreastSurgeon #BreastCancer #CancerSurgeon #SurgicalOncology #CASO #CenterforAdvancedSurgicalOncology

• Presence of clinical lymph node metastasis or distant metastasis (rare)
• Clinically apparent invasion of the recurrent laryngeal nerve (RLN) or trachea
• Diagnosis of aggressive sub type of papillary thyroid carcinoma on cytology (rare)
• Tumor adherent to the trachea, possibly invading
• Tumors located along the course of the RLN
• Associated with other thyroid or parathyroid disease requiring surgery
• Age less than 20 (no current evidence)

#Arrangoiz #ThyroidExpert #ThyroidSurgeon #HeadandNeckSurgeon #EndocrineSurgery @CASO #CenterforAdvancedSurgicalOncology

• The use of an aromatase inhibitor (letrozole) with an inhibitor of the cyclin dependent kinases 4 and 6 (ribociclib):
  • Was compared with aromatase inhibitor alone in postmenopausal women with hormone receptor positive, HER2-negative metastatic breast cancer:
    • In the MONALEESA-2 study:
      • Results showed an improvement in:
        • Progression-free survival (PFS):
          • From 42.2% to 63%
        • Overall response rate:
          • From 37.1% to 52.7%
            • With the addition of ribociclib to letrozole alone
• This regimen was also investigated in pre menopausal women with advanced, hormone receptor-positive breast cancer:
  • Improved PFS compared with placebo plus endocrine therapy
• References:
  • Hortobagi GN, Stemmer SM, Burris HA, Yap YS, Sonke GS, Paluch-Shimon S, et al. Ribociclib as first-line therapy for HR-positive, advanced breast cancer. N Engl J Med. 2016;375(18)1738-1748.
  • Tripathy D, Im SA2, Colleoni M3, Franke F4, Bardia A5, Harbeck Nm et al. Ribociclib plus endocrine therapy for premenopausal women with hormone-receptor-positive, advanced breast cancer (MONALEESA-7): a randomised phase 3 trial. Lancet Oncol. 2018;19(7):904-915.

#Arrangoiz #CancerSurgeon #BreastSurgeon #BreastCancer #Monaleesa2 #Ribociclib #CASO #CenterforADvancedSurgicalOncology

Chemotherapy for a Young Patient with Triple Negative Breast Cancer

• The best choice for chemotherapy for a young patient with a node-positive triple negative breast cancer:
  • Would be dose-dense doxorubicin and cyclophosphamide, followed by paclitaxel, each given for 4 cycles 2 weeks apart with growth factor support:
    • This regimen is supported by results of the:
      • CALGB 9741 study
  • For triple negative breast cancer and node positive disease:
    • The use of an anthracycline-containing regimen is favored compared to a non-anthracycline containing regimen
• References:
  • Citron ML, Berry DA, Cirrincione C, Hudis C, Winer EP, Gradishar WJ, et al. Randomized trial of dose-dense versus conventionally scheduled and sequential versus concurrent combination chemotherapy as postoperative adjuvant treatment of node-positive primary breast cancer: first report of Intergroup Trial C9741/Cancer and Leukemia Group B Trial 9741. J Clin Oncol. 2003;21(8):1431-1439.
  • Blum JL, Flynn PJ, Yothers G, Asmar L, Geyer CE Jr, Jacobs SA et al. Anthracyclines in early breast cancer: The ABC Trials-USOR 06-090, NSABP B-46-I/USOR 07132, and NSABP B-49 (NRG Oncology). J Clin Oncol. 2017;35(23):2647-2655.

Suppression of Ovarian Function Trial (SOFT) Trial

• In the Suppression of Ovarian Function Trial (SOFT) trial:
  • Ovarian function suppression given for five years reduced disease-free survival (DFS) events when added to 5 years of adjuvant tamoxifen:
    • 78.9% to 83.2% DFS at 8 years, hazard ratio (HR) of 0.76, P = .009
  • One-third of women entered in the SOFT trial were randomized to receive the aromatase inhibitor exemestane plus ovarian function suppression:
    • They had an even better disease-free survival
• References:
• Francis PA, Pagani O, Fleming GF, Walley BA, Colleoni M, Lang I, et al. Tailoring adjuvant endocrine therapy for premenopausal breast cancer. N Eng J Med. 2018;379(2):122-137.
• Francis PA, Regan MM, Fleming GF, Lang I, Ciruelos E, Bellet M, et al. Adjuvant ovarian suppression in premenopausal breast cancer. N Engl J Med. 2015;372(5):436-446.

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncologist @CASO @CenterforAdvancedSurgicalOncology #BreastCancer

• The CREATE-X study:
  • Randomly assigned 910 patients:
    • With HER2 negative breast cancer and residual disease after undergoing neoadjuvant chemotherapy to:
      • Standard postsurgical treatment and capecitabine or placebo
  • The primary end point was:
    • Disease-free survival (DFS)
  • Secondary end points included:
    • Overall survival (OS)
  • DFS was longer in the capecitabine group than in the control group:
    • 74.1% vs. 67.6% of the patients were alive and free from recurrence or second cancer at 5 years
  • Among patients with triple-negative disease:
    • DFS was 69.8% in the capecitabine group versus 56.1% in the control group
    • The OS rate was 78.8% versus 70.3%
• Residual disease after completion of neoadjuvant chemotherapy:
  • Is associated with worse outcomes
• References:
  • Masuda N, Lee SJ, Ohtani S, Im YH, Lee ES, Yokota I, et al. Adjuvant capecitabine for breast cancer after preoperative chemotherapy. N Eng J Med. 2017;376(22):2147-2159.
  • Symmans WF, Wei C, Gould R, Yu X, Zhang Y, Liu M, et al. Long-term prognostic risk after neoadjuvant chemotherapy associated with residual cancer burden and breast cancer subtype. J Clin Oncol. 2017;35(10):1049-1060.

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncology #BreastCancer #CASO #CenterforAdvancedSurgicalOncology

• The 21-gene recurrence score assay:
  • Is a gene-expression assay:
    • That provides prognostic and predictive information in hormone receptor positive breast cancer
  • The recurrence score based on the 21-gene assay ranges from:
    • 0 to 100:
      • Is predictive of chemotherapy benefit:
        • When it is higher than 25

• Both tamoxifen and aromatase inhibitors:
  • Have been shown to:
    • Reduce recurrence rates and improve survival in postmenopausal women
  • Although chemotherapy has been shown to be beneficial in many patient subsets:
    • The 21-gene recurrence score was developed:
      • To help ascertain which patients with:
        • ER-positive, node-negative breast cancer:
          • Would be most likely to benefit from chemotherapy in addition to adjuvant tamoxifen
  • In patients with an intermediate recurrence score:
    • The benefit of chemotherapy is unclear
• The Trial Assigning IndividuaLized Options for Treatment (Rx) [TAILORx] trial:
  • Is a randomized prospective trial:
    • That randomized women with ER-positive breast cancer:
      • With a score of 11 to 25 to:
        • Chemotherapy plus endocrine therapy to endocrine therapy alone
    • This trial is closed to accrual, and the results of this trial for this cohort are pending:
      • However:
        • Outcomes data from a subset of 1626 patients with a recurrence score of less than 10:
          • Were recently published
      • These patients were assigned to:
        • Receive endocrine therapy alone without chemotherapy
      • This study reported a 5-year local recurrence rate of:
        • 0.5% in women with a recurrence score of:
          • Less than 10
      • Furthermore:
        • At 5 years:
          • The invasive disease–free survival was:
            • 93.8%
          • The rate of freedom from recurrence of breast cancer at a distant site was:
            • 99.3%
          • At distant or local site was:
            • 98.7%
          • Overall survival rate of:
            • 98%
      • The authors concluded that a favorable gene expression profile:
        • Is associated with a very low rate of recurrence:
          • At 5 years with endocrine therapy alone
• References:
  • Early Breast Cancer Trialists’ Collaborative Group (EBCTCG), Dowsett M, Forbes JF, et al. Aromatase inhibitors versus tamoxifen in early breast cancer: patient-level meta-analysis of the randomised trials. Lancet. 2015;386(10001):1341-1352.
  • Sparano JA, Gray RJ, Makower DF, et al. Prospective validation of a 21-gene expression assay in breast cancer. N Engl J Med. 2015;373(21):2005-2014.
  • Sparano JA et al, N Engl J Med 2018 Sparano JA, Gray RJ, Makower DF, Pritchard KI, Albain KS, Hayes DF, et al. Adjuvant chemotherapy guided by a 21-gene expression assay in breast cancer. N Engl J Med 2018;379(2):111-121.
  • Paik S, Tang G, Shak S, Kim C, Baker J, Kim W, et al. Gene expression and benefit of chemotherapy in women with node-negative, estrogen receptor-positive breast cancer. J Clin Oncol; 2006;24(23):3726-3734.

#Arrangoiz #CancerSurgeon #BreastSurgeon #SurgicalOncologist #CASO #CenterforAdvancedSurgicalOncology #BreastCancer #OncotypeDx