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• TX – Primary tumor cannot be assessed
• Tis – Carcinoma in situ
• T1 – Tumor 2 cm or smaller in greatest dimension
• T2 – Tumor larger than 2 cm but not larger than 4 cm in greatest dimensión
• T3 – Tumor larger than 4 cm in greatest dimensión or extensión to lingual surface of epiglottis
• T4 – Moderately advanced or very advanced local disease
  • T4a – Moderately advanced local disease
    • Tumor invades the larynx, extrinsic muscle of tongue, medial pterygoid, hard palate, or mandible
  • T4b – Very advanced local disease
    • Tumor invades lateral pterygoid muscle, pterygoid plates, lateral nasopharynx, or skull base or encases carotid artery

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• Trastuzumab:
  • Is a monoclonal antibody:
    • That targets the HER2 protein
• After trastuzumab was shown to be efficacious:
  • In the metastatic and adjuvant settings:
    • It was investigated in the neoadjuvant setting:
• In this setting:
  • Significantly increased rates of pCR were observed in HER2+ patients:
    • Treated with trastuzumab in combination with chemotherapy versus chemotherapy alone
• In an initial:
  • Small trial conducted by Buzdar and colleagues:
    • The increase in pCR rates when trastuzumab was combined with chemotherapy:
      • Was so dramatic:
        • 65.2% vs 26.3%
          • p=.016:
          • That the study was terminated early by the data safety monitoring board
• Other trials have investigated dual HER2 targeting:
  • In the neoadjuvant setting:
    • With each regimen having different mechanisms of action and toxicity
• The NeoSphere study:
  • Was a randomized multicenter phase II trial:
    • Investigating the addition of pertuzumab to trastuzumab:
      • With or without docetaxel
  • In patients that received dual HER2-targeting therapy in combination with chemotherapy:
    • There was almost a doubling of the pCR rates in the breast compared to patients that received trastuzumab and chemotherapy alone:
      • 46% vs 29%
        • p=.014
  • In the treatment arm that received dual HER2-targeted therapy without any chemotherapy:
    • The pCR rate:
      • In the breast was 17% and in the axilla was 11%:
        • Suggesting some patients may benefit from HER2-directed therapy alone, without chemotherapy
• Both the CHER-LOB and Tryphaena trials:
  • Show the addition of an anthracycline to dual HER2 blockade:
    • Further improves pCR rates
• To date:
  • Physical exam and imaging (any imaging):
    • Are unable to confirm achievement of a pCR:
      • Therefore, all patients are advised to undergo surgery:
        • There is interest in conducting clinical trials to evaluate MRI with biopsy of the tumor site:
          • To identify patients who may be watched after achieving a complete response to neoadjuvant chemotherapy plus HER2-targeted therapy
• Recent single institution data:
  • Suggest the response to neoadjuvant chemotherapy:
    • May vary according to location:
      • With the axilla demonstrating higher pCR rates than the breast:
        • In all tumor subtypes.
• References:
  • Buzdar AU, Ibrahim NK, Francis D, et al. Significantly higher pathologic complete remission rate after neoadjuvant therapy with trastuzumab, paclitaxel and epirubicin chemotherapy: results of a randomized trial in human epidermal growth factor receptor 2-positive operable breast cancer. J Clin Oncol. 2005;23(16):3676-3685.
  • Untch M, Rezai M, Loibl S, et al. Neoadjuvant treatment with trastuzumab in HER2-positive breast cancer: results from the GeparQuattro study. J Clin Oncol. 2010;28(12): 2024-2031.
  • Gianni L, Eiermann W, Semiglazov V, et al. Neoadjuvant chemotherapy with trastuzumab followed by adjuvant trastuzumab versus neoadjuvant chemotherapy alone, in patients with HER2-positive locally advanced breast cancer (the NOAH trial): a randomized controlled superiority trial with a parallel HER2-negative cohort. Lancet. 2010;375(9712):377-384.
  • Untch M, Fasching PA, Konecny GE, et al. Pathologic complete response after neoadjuvant chemotherapy plus trastuzumab predicts favorable survival in human epidermal growth factor receptor 2-overexpressing breast cancer: results from the TECHNO trial of the AGO and GBG study groups. J Clin Oncol. 2011;29(25):3351-3357.
  • Buzdar AU, Suman VJ, Meric-Bernstam F, et al. Fluorouracil, epirubicin, and cyclophosphamide (FEC-75) followed by paclitaxel plus trastuzumab versus paclitaxel plus trastuzumab followed by FEC-75 plus trastuzumab as neoadjuvant treatment for patients with HER2-positive breast cancer (Z1041): a randomized controlled, phase 3 trial. Lancet Oncol. 2013;14(13):1317-1325.
  • Gianni L, Pienkowski T, Im YH, et al. Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomized multicenter, open-label, phase 2 trial. Lancet Oncol. 2012;13(1):25-32.
  • Baselga J, Bradbury I, Eidtmann H, et al. Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomized, open-label, multi-centre, phase 3 trial. Lancet. 2012;379(9816):633-640.
  • Guarneri V, Frassoldati A, Bottini A, et al. Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol. 2012;30(16): 1989-1995.
  • Rimawi MF, Mayer IA, Forero A, et al. Multicenter phase II study of neoadjuvant lapatinib and trastuzumab with hormonal therapy and without chemotherapy in patients with human epidermal growth factor receptor 2-overexpressing breast cancer: TBCRC 006. J Clin Oncol. 2013;31(14):1726-1731.
  • Schneeweiss A, Chia S, Hickish T, 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.
  • Mamtani A, Barrio AV, King TA, et al. How often does neoadjuvant chemotherapy avoid axillary dissection in patients with histologically confirmed nodal metastases? Results of a prospective study. Ann Surg Oncol. 2016;23(11):3467-3474.

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👉Observation and pharmacologic therapy are less effective and less cost-effective than surgery, even when the patient is considered asymptomatic.”

👉https://jamanetwork.com/journals/jamasurgery/fullarticle/2542667?fbclid=IwAR0ghk6Bmg4UkAhuQ_8wZmFZqAaXtuDkcbgpA32kWfueygaVv7-X1QACIag

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• A combination of the North Central Cancer Treatment Group (NCCTG) N9831 trial and the National Adjuvant Breast and Bowel Project (NSABP) B-31 clinical trials:
  • Showed a:
    • 40% improvement:
      • In disease-free survival
    • 37% improvement:
      • In overall survival:
        • With the addition of a year of trastuzumab:
          • To doxorubicin, cyclophosphamide, and paclitaxel chemotherapy
    • Improvements in disease-free survival and overall survival:
      • Were observed in all patients:
        • Independent of hormone receptor status and extent of nodal involvement
• The duration of trastuzumab therapy has been debated:
  • The Herceptin Adjuvant (HERA) trial:
    • Evaluated 1 year of therapy versus 2 years of therapy:
      • Did not show a significant difference:
        • In disease-free survival and overall survival between the two groups
  • The Protocol of Herceptin Adjuvant with Reduced Exposure, a Randomized Comparison of 6 Months vs 12 Months in All Women Receiving Adjuvant Herceptin (PHARE) trial:
    • Evaluated 6 months of trastuzumab compared to 12 months:
      • At 3.5-year follow-up:
        • The shorter trastuzumab course did not have a worse survival outcome compared to the 12-month course
  • A Cochrane meta-analysis of eight trials:
    • Including more than 11,900 patients:
      • With early and locally advanced HER2-positive breast cancer:
        • Also found improvements in:
          • Disease-free survival (HR 0.66) and overall survival (HR 0.60) with:
            • Chemotherapy plus trastuzumab versus chemotherapy alone or trastuzumab alone regimens
• Two small trials administering trastuzumab for less than six months:
  • Did not differ from trials with longer treatment duration and had less trastuzumab-associated toxicities:
    • However, given these studies’ small cohort size and short follow-up:
      • 12 months of trastuzumab treatment remains standard therapy

REFERENCES

1. Perez EA, Romond EH, Suman VJ, et al. Trastuzumab plus adjuvant chemotherapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol. 2014;32(33):3744-3752.
2. Goldhirsch A, Gelber RD, Piccart-Gebhart MJ, et al. 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomised controlled trial. Lancet. 2013;382(9897):1021-1028.
3. Pivot X, Romieu G, Debled M, et al. 6 months versus 12 months of adjuvant trastuzumab for patients with HER2-positive early breast cancer (PHARE): a randomised phase 3 trial. Lancet Oncol. 2013;14(8):741-748.
4. Moja L, Tagliabue L, Balduzzi S, et al. Trastuzumab containing regimens for early breast cancer. Cochrane Database Syst Rev. 2012;4:CD006243.

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• Peripheral neuropathies:
  • Induced by chemotherapy are an increasingly frequent problem
    • Typically, the appearance of drug-induced peripheral neurotoxicities is:
    • Predominantly sensory:
      • Length-dependent
      • Develop after cumulative doses
  • However:
    • Immediate neurologic effects:
      • Can appear with taxane-based therapy and platin derivatives
  • Paclitaxel:
    • Is slightly more neurotoxic than docetaxel
  • Most chemotherapy-induced neuropathies:
    • Are sensory:
      • Tingling or numbness in the feet or fingers:
        • Is often an early sign
  • The risk of developing severe taxane-induced chemotherapy-induced peripheral neuropathies:
    • Is related to the treatment interval:
      • The use of an albumin-bound paclitaxel formulation:
        • Abraxane:
          • Seems to be less neurotoxic
• Cardiotoxicity:
  • Is more common after doxorubicin-based chemotherapy regimens
  • In this setting:
    • Cardiomyopathy can be acute or chronic:
      • In the acute setting:
        • Doxorubicin cardiotoxicity:
          • Can occur within 2 to 3 days of its administration
        • Occurs with an incidence of:
          • Approximately 11%
        • Patients may experience:
          • Chest pain, palpitations, paroxysmal nonsustained supraventricular tachycardia, and premature atrial and ventricular beats
        • It is hypothesized that this cardiomyopathy may be due to:
          • Reversible myocardial edema
    • Chronic doxorubicin cardiotoxicity:
      • Occurs in about:
        • 1.7% of patients
      • Is usually evident:
        • Within 30 days of administration of its last dose:
          • But can occur up to 10 years later
  • The incidence of doxorubicin cardiomyopathy is primarily related to its dose:
    • Is reported to be about:
      • 4% when the dose is 500 to 550 mg/m2
      • 18% when 551 to 600 mg/m2
      • 36% when the dose exceeds 600 mg/m2

REFERENCES

1. Hahn KM, Johnson PH, Gordon N, et al. Treatment of pregnant breast cancer patients and outcomes of children exposed to chemotherapy in utero. Cancer. 2006;107(6):1219-1226.
2. Conlin AK, Seidman AD, Bach A, et al. Phase II trial of weekly nanoparticle albumin-bound paclitaxel with carboplatin and trastuzumab as first-line therapy for women with HER2-overexpressing metastatic breast cancer. Clin Breast Cancer. 2010;10(4):281-287.
3. Chatterjee K, Zhang J, Honbo N, Karliner JS. Doxorubicin cardiomyopathy. Cardiology. 2010;115(2):155–162.

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• Data from the Early Breast Cancer Trialists’ Collaborative Group:
  • Meta-analysis of adjuvant systemic therapy trials begun in or before 1995:
    • Show a 30% relative reduction:
      • In breast cancer-related mortality:
        • Associated with adjuvant hormonal therapy and with adjuvant chemotherapy
  • Reduced ratesof:
    • Ipsilateral local recurrence, contralateral cancers, and distant metastases in treated patients:
      • Suggest there is eradication of occult residual disease in many patients
  • The absolute survival benefit of adjuvant therapy:
    • Is greater in node-positive than in node-negative patients
  • The absolute survival benefit of chemotherapy:
    • Is greater for younger (less than 50 years of age) than for older women (50 to 69 years of age)
• References:
  • Early Breast Cancer Trialists’ Collaborative Group (EBCTCG). Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet. 2005;365(9472):1687-1717.
  • Berry DA, Cronin KA, Plevritis SK, et al. Effect of screening and adjuvant therapy on mortality from breast cancer. N Engl J Med. 2005;353(17):1784-1792.

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• The definition of menopause:
  • Is defined as the permanent cessation of menses
• The use of the term in breast cancer clinical trials has resulted in a variety of definitions, including:
  • A profound and permanent decrease in ovarian estrogen synthesis
• According to the NCCN guidelines:
  • Reasonable criteria for determining menopause includes the following:
    • History of bilateral oophorectomy
    • Age greater than or equal to 60
    • Age less than 60 and amenorrheic for 12 or more months:
      • In the absence of chemotherapy, tamoxifen, toremifene, or ovarian suppression and follicle-stimulating hormone (FSH) and estradiol in the postmenopausal range
    • If taking tamoxifen or toremifene, and age less than 60:
      • Then FSH and plasma estradiol level in postmenopausal ranges
• It is not possible to assign menopausal status:
  • To women who are receiving an LHRH agonist or antagonist
• In women premenopausal at the beginning of adjuvant chemotherapy:
  • Amenorrhea is not a reliable indicator of menopausal status:
    • As ovarian function may still be intact or resume despite anovulation / amenorrhea after chemotherapy:
      • For these women with therapy-induced amenorrhea:
        • Oophorectomy or serial measurement of FSH and/or estradiol:
          • Are needed to ensure postmenopausal status:
            • If the use of aromatase inhibitors is being considered as endocrine therapy
• References:
  • Yu B, Douglas N, Ferrin MJ, et al. Changes in markers of ovarian reserve and endocrine function in young women with breast cancer undergoing adjuvant chemotherapy. Cancer. 2010;116(9):2099-2105.
  • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines for Oncology: Breast Cancer. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp Published January 2016. Accessed January 31, 2017.

#Arrangoiz #BreastSurgeon #BreastCancer #CancerSurgeon #SurgicalOncologist

• Women with early-stage breast cancer:
  • Typically undergo surgery up front
• While women with more advanced disease:
  • Larger tumors
  • Locally advanced tumors
  • High grade tumors
  • Lymph node positive
  • Triple-negative breast cancer
  • HER2-positive breast cancer:
    • May benefit from neoadjuvant therapy
• The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) trial:
  • Randomized 330 postmenopausal women with:
    • ER-positive breast cancer
    • Invasive breast cancer
    • Non-metastatic breast cancer
    • Operable breast cancer
    • Locally advanced potentially operable breast cancer:
      • To neoadjuvant:
        • Tamoxifen, anastrozole, or a combination of tamoxifen and anastrozole:
          • For three months
  • Among patients enrolled:
    • The median age was 73
    • The median tumor size was 4 cm
    • No chemotherapy was given
  • Overall response rates:
    • Were similar among the three arms:
      • At a median of 13 weeks
  • In patients who were assessed as requiring mastectomy at baseline (n = 124):
    • 44% received breast-conserving surgery after anastrozole and
    • 31% after tamoxifen
      • p = .23
• Importantly:
  • pCR is rare:
    • With neoadjuvant endocrine therapy
• There have not been any Phase III randomized trials:
  • Comparing neoadjuvant chemotherapy to neoadjuvant endocrine therapy
• A number of clinical trials have reported:
  • Conversion rates of mastectomy to breast-conserving surgery:
    • Ranging from 30% to 88%
• In the ACOSOG Z1031 trial:
  • Ki67 reduction:
    • Was associated with response to:
      • Neoadjuvant aromatase inhibitor therapy
  • Tumor Ki67 levels determined after initiation:
    • Of neoadjuvant endocrine treatment:
      • Are more prognostic than baseline analysis
• Ellis et al described a:
  • Preoperative endocrine prognostic index (PEPI) score:
    • In which Ki67 data have been integrated into a post-treatment model that also includes:
      • Pathologic stage and ER levels
        • Patients with pathologically node-negative, T1 or T2 disease with a:
          • Fully suppressed Ki67 level (2.7% or 1% on a natural log scale) and persistent ER expression:
            • After completion of neoadjuvant endocrine therapy (PEPI of 0):
              • Were found to have such a low risk of relapse that:
                • Adjuvant chemotherapy after neoadjuvant endocrine therapy:
                  • May not be necessary
• In the letrozole vs tamoxifen P024 trial:
  • The relationship between ER expression by Allred score and log odds of response fit a linear model that was significant by logistic regression
• A recent systematic review and meta-analysis of 20 prospective, randomized, neoadjuvant clinical trials:
  • That reported response rates concluded:
    • Neoadjuvant endocrine therapy with aromatase inhibitors resulted in a similar clinical and radiological response rate and breast conservation surgery rate but:
      • With lower toxicity than combination chemotherapy
  • Patients treated with aromatase inhibitors:
    • Had a higher clinical tumor response rates than those treated with tamoxifen
  • Overall, the pathologic complete response was:
    • Less than 10% in the review
• References:
  • Smith IE, Dowsett M, Ebbs SR, et al. Neoadjuvant treatment of postmenopausal breast cancer with anastrozole, tamoxifen, or both in combination: The Immediate Preoperative Anastrozole, Tamoxifen, or Combined with Tamoxifen (IMPACT) multicenter double-blind randomized trial. J Clin Oncol. 2005;23(22):5108-5116.
  • Allred DC, Harvey JM, Berardo M, Clark GM. Prognostic and predictive factors in breast cancer by immunohistochemical analysis. Mod Pathol. 1998;11(2):155-168.
  • Ellis MJ, Suman VJ, Hoog J, et al. Randomized phase II neoadjuvant comparison between letrozole, anastrozole, and exemestane for postmenopausal women with estrogen receptor–rich stage 2 to 3 breast cancer: clinical and biomarker outcomes and predictive value of the baseline PAM50-based intrinsic subtype – ACOSOG Z1031. J Clin Oncol. 2011;29(17):2342-2349.
  • Olson JA Jr, Budd GT, Carey LA, et al. Improved surgical outcomes for breast cancer patients receiving neoadjuvant aromatase inhibitor therapy: Results from a multicenter phase II trial. J Am Coll Surg. 2009;208(5):906-914.
  • Dowsett M, Smith IE, Ebbs SR, et al. Short-term changes in Ki-67 during neoadjuvant treatment of primary breast cancer with anastrozole or tamoxifen alone or combined correlate with recurrence free survival. Clin Cancer Res. 2005;11(2 Pt 2):951s-958s.
  • Eiermann W, Paepke S, Appfelstaedt J, et al. Preoperative treatment of postmenopausal breast cancer patients with letrozole: A randomized doubleblind multicenter study. Ann Oncol. 2001;12(11):1527-1532.

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• Pertuzumab:
  • Is approved for use preoperatively in advanced disease and in the metastatic setting
• Trastuzumab:
  • Is approved for use in neoadjuvant, adjuvant, and metastatic settings
• Ado-trastuzumab-emtansine and lapatinib:
  • Are approved for use in the metastatic setting:
    • Among patients who have progressed on previous lines of systemic chemotherapy, including trastuzumab
• Lapatinib:
  • Is an oral small molecule receptor tyrosine kinase inhibitor of both:
    • HER2 and EGFR
• Trastuzumab and pertuzumab:
  • Are humanized monoclonal antibodies:
    • That target the extracellular HER2 domain
  • However, pertuzumab:
    • Binds to a different HER2 epitope than trastuzumab:
      • Resulting in more HER2 blockade when they are given together
• Ado-trastuzumab-emtansine:
  • Is a HER2-antibody drug conjugate:
    • That incorporates trastuzumab with emtansine:
      • A microtubule inhibitor DM1:
    • The conjugate:
      • Which is linked via a stable thioether linker:
        • Allows for selective delivery into HER2 overexpressing cells:
          • Resulting in cell cycle arrest and apoptosis

REFERENCES

1. Lin JJ, Cardarella S, Lydon CA, et al. Five-year survival in EGFR-mutant metastatic lung adenocarcinoma treated with EGFR-TKIs. J Thorac Oncol. 2016;11(4):556-565.
2. Weickhardt AJ, Price TJ, Chong G, et al. Dual targeting of the epidermal growth factor receptor using the combination of cetuximab and erlotinib: preclinical evaluation and results of the phase II DUX study in chemotherapy-refractory, advanced colorectal cancer. J Clin Oncol. 2012;30(13):1505-1512.
3. Jiang H, Rugo HS. Human epidermal growth factor receptor 2 positive (HER2+) metastatic breast cancer: how the latest results are improving therapeutic options. Ther Adv Med Oncol. 2015;7(6):321-339.

#Arrangoiz #BreastCancer #CancerSurgeon #SurgicalOncology #BreastSurgeon

• The recommended initial treatment regimen:
  • For premenopausal women with:
    • De novo stage IV ER-positive breast cancer is:
      • Endocrine therapy + ovarian ablation/suppression
• With ovarian ablation / suppression:
  • The choice of endocrine therapy becomes similar to that of postmenopausal women and may include:
    • Tamoxifen or an aromatase inhibitor
• New research focusing on the:
  • Cyclin-dependent kinase 4/6 inhibitors (CDK):
    • Is emerging in this setting as well:
      • And could be added to endocrine therapy with ovarian function suppression
• Investigation began:
  • In the postmenopausal patient population
• The PALOMA-1 trial:
  • Randomized postmenopausal women with advanced-stage, ER-positive, HER2-negative breast cancer to either:
    • Letrozole alone or letrozole in combination with palbociclib (CDKs 4 and 6 inhibitor):
      • Who had not received any systemic therapy
  • Median progression-free survival was:
    • 10.2 months versus 20.2 months:
      • In the letrozole group versus the palbociclib plus letrozole groups respectively:
        • p=0.0004
  • This phase 2 study:
    • Led to the FDA approval of palbociclib:
      • For treatment of postmenopausal women with ER-positive, HER2-negative:
        • Metastatic breast cancer
• Phase 3 studies are ongoing:
  • However, the PALOMA-3 trial:
    • Randomized 521 women with ER-positive, HER2-negative metastatic breast cancer:
      • Who had progressed on prior endocrine therapy to:
        • Palbociclib plus fulvestrant or fulvestrant plus placebo
    • Median progression-free survival:
      • Was 9.5 months in those receiving fulvestrant plus palbociclib versus 4.6 months in those receiving fulvestrant plus placebo
        • p<0.0001
    • These data suggest an emerging role for CDK inhibitors:
      • In women with ER-positive, HER2-negative advanced disease
• In the metastatic setting:
  • Neither radiation nor surgical resection of the primary tumor at diagnosis:
    • Have conclusively been shown to:
      • Improve overall survival
  • This question has been evaluated in several retrospective and large database series concluding optimistic results:
    • However:
      • These data are limited by significant selection bias
• Two randomized controlled trials also address this question:
  • Badwe et al randomly assigned 350 patients with de novo stage IV breast cancer:
    • To receive locoregional therapy to the primary breast tumor and axilla or to no locoregional treatment
      • They stratified patients by:
        • Site of distant metastasis
        • Number of distant metastases
        • Hormone receptor status
    • Median overall survival was:
      • 19.2 months:
        • In those randomized to locoregional treatment and
      • 20.5 months:
        • In those in the no-locoregional treatment group
          • p=0.79
    • The investigators concluded:
      • There was no evidence that local treatment of the primary tumor:
        • Affects overall survival in patients with de novo stage IV disease who have responded chemotherapy
• Second, Soran et al randomly assigned 274 women with treatment-naive stage IV breast cancer:
  • To local regional surgery plus systemic therapy versus systemic therapy alone
  • At a median follow-up of 40 months:
    • Overall survival was:
      • 46 months in the surgery group compared to only 36 months in the systemic therapy group
  • Unplanned subgroup analyses were performed:
    • And concluded overall survival was statistically higher in:
      • The surgery group than in the systemic therapy group in hormone receptor-positive, HER2-negative patients
        • HR: 0.64, p=0.01
      • In patients less than 55 years
        • HR 0.57, p = 0.006
      • In those with solitary bone-only metastasis
        • HR: 0.47, p = 0.04
  • The authors concluded:
    • There may be a benefit to locoregional surgery
• In the US, E2108 is an ongoing randomized trial addressing this question as well
• References:
  • Badwe R, Hawaldar R, Nair N, et al. Locoregional treatment versus no treatment of the primary tumour in metastatic breast cancer: an open-label randomised controlled trial. Lancet Oncol. 2015;16(13):1380-1388.
  • National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines for Oncology: Breast Cancer. https://www.nccn.org/professionals/physician_gls/f_guidelines.asp Published January 2016. Accessed January 31, 2017.
  • Partridge AH, Rumble RB, Carey LA, et al. Chemotherapy and targeted therapy for women with human epidermal growth factor receptor 2-negative (or unknown) advanced breast cancer: American Society of Clinical Oncology Clinical Practice Guideline. J Clin Oncol. 2014;32(29):3307-3329.
  • Finn RS, Crown JP, Lang I, 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.
  • Cristofanilli M, Turner NC, Bondarenko I, et al. Fulvestrant plus palbociclib versus fulvestrant plus placebo for treatment of hormone-receptor-positive, HER2-negative metastatic breast cancer that progressed on previous endocrine therapy (PALOMA-3): final analysis of the multicentre, double-blind, phase 3 randomised controlled trial. Lancet Oncol. 2016;17(4):425-439.
  • Atilla Soran, Vahit Ozmen, Serdar Ozbas, et al. A randomized controlled trial evaluating resection of the primary breast tumor in women presenting with de novo stage IV breast cancer: Turkish Study (Protocol MF07-01). J Clin Oncol. 2016;34(suppl; abstr 1005).

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