Author: Rodrigo Arrangoiz MS, MD, FACS, FSSO

• 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.

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• 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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• The 21-gene recurrence score assay (Oncotype DX):
  • Is a reverse-transcriptase-polymerase-chain-reaction assay of:
    • 16 prospectively selected genes and 5 reference genes
• Analysis is performed in:
  • Paraffin-embedded tumor tissue
• This assay was developed from:
  • NSABP B-14 and validated with data and specimens from NSABP B-20
• It estimates the 10-year risk of distant recurrence:
  • By categorizing results into:
    • Low-risk (RS<18) group
    • Intermediate-risk (RS 18-30) group
    • High-risk (RS>30) group
• A low recurrence score:
  • Predicts little benefit of chemotherapy
• The 21-gene recurrence score assay is proven to be prognostic for women with:
  • Node-negative
  • ER-positive breast cancer:
    • Treated with tamoxifen
• Retrospective data obtained via optional tumor banking:
  • In accordance with the SWOG 8814 trial:
    • Which demonstrated postmenopausal women with node-positive ER-positive tumors achieved:
      • Superior survival when cyclophosphamide, doxorubicin, and fluorouracil was given before tamoxifen
  • The SWOG 8814 trial:
    • Allowed for retrospective assessment of recurrence score on DFS by treatment group
    • Analysis demonstrated the recurrence score results:
      • To be both prognostic and predictive of benefit to adjuvant chemotherapy:
        • As there was no added benefit to adjuvant systemic chemotherapy:
          • In women with low recurrence scores and
          • An improvement of DFS:
            • In those with high recurrence scores
• These hypothesis-generating results serve as preliminary basis:
  • For the RxPonder trial:
    • Which is currently enrolling as a phase III trial:
      • Randomizing women with hormone receptor-positive and HER2-negative breast cancer involving 1 to 3 lymph nodes and a 21-gene assay recurrence score of 25 or less:
        • To endocrine therapy alone versus chemotherapy followed by endocrine therapy
• The 21-gene recurrence score:
  • Is not used in patients with HER2-positive breast cancer

REFERENCES

1. Paik S, Shak S, Tang G, et al. A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med. 2004;351(27):2817-2826.
2. Paik S, Tang G, Shak S, 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.
3. Albain KS, Barlow WE, Shak S, et al. Prognostic and predictive value of the 21-gene recurrence score assay in postmenopausal women with node-positive, oestrogen-receptor-positive breast cancer on chemotherapy: a retrospective analysis of a randomised trial. Lancet Oncol. 2010;11(1):55-65.
4. Ramsey SD, Barlow WE, Gonzalez-Angulo AM, et al. Integrating comparative effectiveness design elements and endpoints into a phase III, randomized clinical trial (SWOG S1007) evaluating oncotypeDX-guided management for women with breast cancer involving lymph nodes. Contemp Clin Trials. 2013;34(1):1-9.

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• In patients with metastatic HER2-positive breast cancer:
  • The addition of pertuzumab to trastuzumab and chemotherapy:
    • Improves progression-free survival
• The Clinical Evaluation of Pertuzumab and Trastuzumab (CLEOPATRA) trial:
  • Randomized:
    • 808 women with HER2-positive metastatic breast cancer:
      • To trastuzumab and docetaxel plus pertuzumab versus placebo
    • Median 50-month follow-up
    • Results:
      • The trastuzumab, docetaxel, pertuzumab arm:
        • Was associated with a 15.7-month improvement:
          • In median overall survival
        • A 6.3-month improvement:
          • In median progression-free survival:
      • Compared to the trastuzumab, docetaxel, placebo arm:
        • Single-agent trastuzumab:
          • Results in reduced efficacy and should only be reserved for patients:
            • Who elect to avoid chemotherapy or
            • For those whom are poor candidates for chemotherapy
• Trastuzumab plus anthracyclines (doxorubicin):
  • Are effective:
    • But there is higher cardiotoxicity with this combination
• BCIRG 007:
  • Showed that multi-agent chemotherapy plus trastuzumab:
    • Paclitaxel, carboplatin, and trastuzumab:
      • Does not increase overall survival:
        • Compared to single-agent chemotherapy:
          • With docetaxel plus trastuzumab in patients with metastatic HER2-positive breast cancer
• References:
  • Baselga J, Cortes J, Kim SB, et al. Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med. 2012;366(2):109-119.
  • Swain SM, Kim SB, Cortes J, et al. Pertuzumab, trastuzumab, and docetaxel for HER2-positive metastatic breast cancer (CLEOPATRA study): overall survival results from a randomised, double-blind, placebo-controlled, phase 3 study. Lancet Oncol. 2013;14(6):461-471.
  • Swain SM, Baselga J, Kim SB, et al. Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med. 2015;372(8):724-734.
  • Valero V, Forbes J, Pegram MD, et al. Multicenter phase III randomized trial comparing docetaxel and trastuzumab with docetaxel, carboplatin, and trastuzumab as first-line chemotherapy for patients with HER2-gene-amplified metastatic breast cancer (BCIRG 007 study): two highly active therapeutic regimens. J Clin Oncol. 2011;29(2):149-156.

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• The major determinant of overall survival:
  • In patients with inflammatory breast cancer:
    • Is the high risk of metastatic disease
• Use of preoperative therapy in this setting:
  • Is to target any micrometastatic disease
  • To improve operability and surgical margins
  • To to evaluate response to chemotherapy
• Neoadjuvant chemotherapy, surgery, and radiation therapy:
  • Remains the standard of care for this disease
• A modified radical mastectomy without reconstruction:
  • Is the preferred treatment in this patient population:
    • Breast-conserving surgery:
      • Should not be offered:
        • Regardless of response to treatment
• References:
  • Perez CA, Fields JN, Fracasso PM, et al. Management of locally advanced carcinoma of the breast. II. Inflammatory carcinoma. Cancer. 1994;74(1 Suppl):466-476.
  • Rueth NM, Lin HY, Bedrosian I, et al. Underuse of trimodality treatment affects survival for patients with inflammatory breast cancer: an analysis of treatment and survival trends from the National Cancer Database. J Clin Oncol. 2014;32(19):2018-2024.

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