Controversies in Breast Cancer

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I Have Breast Cancer Now What? Katherine Gale FRACS Oncoplastic Breast Surgeon Controversies in Breast Cancer Katherine Gale FRACS

Oncologic Controversies Margins in BCS Nipple Sparing Mastectomy:? Safe Contralateral Mx Management of Axilla Radiotherapy; IORT/WBRT/APBRT MRI Generally In lobular breast cancer BRCA

Reconstruction Controversies. Partial breast recon What is this??? Cosmetic surgery?? Patient selection Access to procedures Who s qualified to do it new procedures Timing of reconstruction Funding esp in private sector Surveillance do oncoplastic procedures affect cancer surveillance?

1. Margins

2. NSM

2. NSM

2. NSM 345 articles reviewed LR after therapeutic NSM <5% <1% cancer in retained nipple after risk reducing NSM Partial necrosis up to 16%, full necrosis up to 8% Rusby, J. E., Smith, B. L., & Gui, G. P. H. (2010). Nipple sparing mastectomy. British journal of surgery, 97(3), 305-316.

3. Axilla We struggle to take away treatment Examples of changes in BC treatment and residual disease BCS considered radical when first introduced in NSABP- B06 BCS didn t stop when EBCTCG reported ¼ LR resulted in BC death Occult mets for years - left untreated Micromets now left untreated Macromets Z11 suggests we can leave surgically, but robust adjuvant Rx essential. Pt suitability problems.

3. Axilla ACOSOG ZOO10 Clinically and USS node -, SNB+ ITCs and micromets -> not clinically significant (observe after SNB) If SNB+ with limited macromets; ANC does not contribute to improved survival or LRR in BCS (? leave at SNB) ACOSOG ZOO11 Inv Br Ca 5 cm or less treated with BCS Clinically node negative, with 1-2 +ve SNB macromets Randomised; standard adjuvant therapy(rt/chemo/endocrine Rx) vs ANC + Adjuvant therapy NB. Tangential field for BCS covers most of axilla in US practice and high rate of chemo given?applicability to general BC patient population

3. Axilla Important question is: What is % nodal macromet burden found on SNB/USS that accurately predicts presence of extra positive axillary nodes i.e. those patients that would benefit from an ANC. Z011 may be irrelevant if not giving systemic Rx (97% had adjuvant treatment, 75% had chemo!)

3. Axilla ANC or RT in SNB+ Amaros Trial Small (<3cm) tumours. Clinically -ve but snb +ve No benefit of RT vs ANC for survival Less lymphoedema with RT 2* difference in LRR (does this equate to poorer survival later?) Underpowered POSNOC Trial POSNOC - POsitive Sentinel NOde: adjuvant therapy alone versus adjuvant therapy plus Clearance or axillary radiotherapy. RCT of axillary treatment in women EBC who have metastases in one or two sentinel nodes 10yrs until we will get results.

RT: IORT TARGIT-A Trial Non-inferiority RCT After BCS, 90% LR in index quadrant despite the presence of multicentric cancers. IORT might be adequate for selected patients. 2 arms; IORT - tumor bed irradiation 20 Gy to surgical margins using soft x-rays (50 kv) delivered with the Intrabeam Photon Radiosurgery System (Zeiss Inc, Oberkochen, Germany). 1113 patients IORT and 1119 WBRT Kaplan-Meier estimate of LR in conserved breast at 4 years 1 20% (95% CI 0 53 2 71) in IORT and 0 95% (0 39 2 31) in WBRT (difference 0 25%, 1 04 to 1 54; p=0 41). Vaidya, Jayant S., et al. "Targeted intraoperative radiotherapy versus whole breast radiotherapy for breast cancer (TARGIT-A trial): an international, prospective, randomised, non-inferiority phase 3 trial." The Lancet 376.9735 (2010): 91-102.

IORT Eligibility 50yrs+ T1 tumours Node negative ER+

MRI Sensitive, non-specific Increased mastectomy rates; no benefit margin control No improvement in survival when used on ALL invasive cancers (Morrow/Houssami et al) Useful in; Discordant clinical/radiological scenarios BRCA mutation Assessment of neoadj chemo effect

MRI ORIGINAL RESEARCH MRI and clinical outcomes in lobular breast cancer; What you can t see won t hurt you? Gale KL a*, Vather R a, Chin P, Harman R a a Department of Surgical Oncology, North Shore Hospital, Waitemata DHB Auckland, New Zealand The corresponding author is not a recipient of a research scholarship. *Corresponding author; Miss Katherine Gale. Tel +64 870080 Level 8, North Shore Hospital, 124 Shakespeare Road Takapuna AUCKLAND CITY 0622, Private Bag 93-503 Takapuna AUCKLAND CITY 0740 E mail address: kathgale@gmail.com

MRI

Breast cancer treatment, prevention and surveillance pathways for BRCA-mutation carriers at NBI Gale KL, Caracappa D, James R, Scott NAL, Macmillan RD

Mutation Carrier Summary NBI 259 BRCA positive 154 BRCA1 105 BRCA2 148 Breast Asymptomatic Patients 111 Primary Breast Cancer 90 Breast Screening 46 BRCA1 44 BRCA2 58 Risk Reducing Surgery 38 BRCA1 20 BRCA2 111 Oncologic Breast Surgery 70 BRCA1 41 BRCA2

BRCA Total (n=111) Mean age Mean size (mm) 40.7 22.9 2.94 Grade 1; 2 Grade 2; 11 Grade 3; 96 Unknown; 2 (88% Gd3) Grade Node Status VI Mean NPI 1.45 Stage 1; 72 Stage 2; 28 Stage 3; 8 Unknown; 3 (33% node +) Present 32 (29%) Absent 69 (62%) Unknown 10 (9%) 4.75 Screen detected (n=21) 46.7 18.5 2.76 Grade 1; 1 Grade 2; 3 Grade 3; 17 (81% Gd3) 1.10 Stage 1; 19 Stage 2; 2 (10% node +) Present 6 (29%) Absent 13 (62%) Unknown 2 (9%) 4.41 Symptomatic (n=90) 39.3 23.8 2.88 Grade 1; 1 Grade 2; 8 Grade 3; 79 Unknown; 2 (90% Gd3) 1.48 Stage 1; 48 Stage 2; 31 Stage 3; 8 Unknown; 3 (45% node +) Present 36 (40%) Absent 56 (62%) Unknown 8 (18%) 4.85

Treatment Breast Cancer Operation 78 % Post Mastectomy RxT 78 78 70 41 WLE Mastectomy 76 74 72 70 71 70 63% mastectomy (initial Mx 47%/WLE 53%) 68 66 BRCA1 BRCA2 Symptomatic Screening 73% Post-Mx radiotherapy

Chemotherapy Chemotherapy indicated in 95% all cases 98 96 94 92 90 88 86 97 90 94 90

BRCA Mode of Presentation Mean age (yrs) Size Average Grade/ Node Status Mean NPI NPI Predictn 10yr survival 10yr Survival* BRCA 1 Screening 43 17 3/+ 4.41 77% 89% Symptomatic 39 24 3/+ 4.85 71% 86% BRCA 2 Screening 51 21 2/- 3.97 82% 90% Symptomatic 41 23 3/+ 4.95 69% 91% * www.lifemath.net/cancer/breastcancer/outcome; With Chemotherapy in ER- patients, or Chemotherapy & Endocrine Rx in ER+ patients

58 Prophylactic Surgery Mean age 39 yrs No breast cancers in 125 096 woman-years follow up (mean 6.6 years) 81% Implant based reconstruction Prophylactic Mastectomy Reconstructions 60 47 40 20 0 Implant LD DIEP 9 2

Conclusions 259 BRCA mutation carriers through NBI family history service Treatment of BRCA-related breast cancer is very likely to involve chemotherapy and radiotherapy, both for symptomatic and screen-detected cases Risk estimates of developing life-threatening breast cancer may be useful BRCA 1 risk approx 1.5X BRCA 2 risk if Sxic No proven method to reduce this risk other than surgery

Reconstruction Controversies. Reconstruction; Partial breast recon What?? Patient selection Access to procedures who s qualified to do it timing of Funding esp in private sector Surveillance

Surgery

Is oncoplastic breast surgery really necessary?

Oncoplastic Breast Surgery Surgery for breast cancer that optimises both the oncological and FOR THE cosmetic outcomes

SELECTION Important! Simple lumpectomy (Partial Mastectomy) +/- Level I Oncoplastic closure Level II Oncoplastic Closure; Volume Displacement Therapeutic Mammaplasty Volume Replacement Chest wall perforator Flaps Fat grafting

Aesthetic outcome BCS Negatively influenced by; increasing specimen weight and % volume excision decreasing breast size medial and inferior tumour position Radiotherapy, boost of radiotherapy to tumour bed re-excision procedures and increasing scar length 12,15,16. large breasted women; increased adiposity combined with greater dose inhomogeneity may contribute to fat necrosis and fibrosis, resulting in impaired long term cosmetic outcomes.

Aesthetic outcome Pronounced breast asymmetry after BCS is significantly correlated with poor psychosocial functioning Constant reminder of the disease and treatment experience, leading to impaired psychological adjustment Women with pronounced asymmetry are more likely to exhibit depressive symptoms.oncoplastic techniques

BRA Breast Retraction Assessment Score score = symmetry Absolute vs Relative BRA Score The Breast Cancer Conservative Treatment Aesthetic Results (BCCT.core Cardoso et al. Recommendations for the aesthetic outcome of breast cancer conservative treatment. Breast Cancer Res Treat. Jan 2012

The reality.

Fat grafting

Mastectomy Simple Mastectomy Skin Sparing Mastectomy Nipple Sparing Mastectomy +/- Reconstruction Immediate/Delayed Autologous (own tissue) Prosthetic (implants); 1->3 Stage

Imaging Post Therapeutic mammaplasty Gale KL, Taneja S, Evans AJ, James JJ, Cornford EJ, McCulley SJ, Macmillan RD Nottingham Breast Institute, Nottingham City Hospital, Hucknall Road, Nottingham NG5 1PB, UK

Aim Evaluate the mammographic appearances after BTM Frequency of additional imaging and biopsies Compare these rates to matched controls of woman who had a WLE only

Patients Timeline: Jan 2001 - June 2008 (90 months, 7.5yrs) 264 patients Retrospective analysis & film review 3 Radiologists 2 Oncoplastic breast surgeons Observations recorded for; Ipsilateral BTM (cancer) Contralateral BTM breast Ipsilateral WLE (cancer) Contralateral WLEbreast

Calcification

Additional Imaging a Comparison made between cancer side breasts

Biopsy a Comparison made between cancer side breasts b Comparison between non-cancer breasts

The Impact of Partial Breast Reconstruction Using Reduction Techniques on Postoperative Cancer Surveillance Losken, Albert M.D.; Schaefer, Timothy G. M.D.; Newell, Mary M.D.; Styblo, Toncred M. M.D. PRS: July 2009 vol 124-issue 1- pp 9-17 Oncoplastic (TM) Number No. 17 17 Age Pathology Mean Range DCIS Invasive 61 44-81 1 16 IBLR No. 1 1 WLE 52 38-72 7 10 Follow-up yrs 5.9 6.3 P value Freq. USS No. (%) 7 (41%) 0.17 USS/yr Freq. Bx No. (%) 9 (53%) 0.25 Bx/yr 8 (47%) 0.09 USS/yr 3 (18%) 0.03Bx/yr 0.29 0.015*

Conclusions Predictable mammographic appearances after BTM, comparable to WLE No significant difference in the rate of additional imaging or biopsies in the BTM group compared to WLE BTM does not interfere with cancer surveillance for the experienced Radiologist

Summary Incorporate reconstruction into oncologic decision making for best outcomes reduced surgical exposure and better aesthetic outcomes Many controversies; MDTs essential Work together for better patient outcomes

Questions?