Controversies in Surgical Approach to Breast Cancer

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Suebwong Chuthapisith MD, PhDAssistant Professor, Department of Surgery

Faculty of Medicine Siriraj Hospital , Mahidol University, THAILAND

Controversy 1 : Detecting lesion in dense breast

Controversy 2 : How to deal with positive SLNB?

Controversy 3 :Use of IORT following BCS

Controversies in breast cancer: surgeons’ concern

In screening and detecting of breast cancer, mammography is a standard and is recommended

(annually) for women age > 40 yrs

Lee et al. J Am Coll Radiol 2010;7:18.

However, detecting small cancer with mammography alone may not be adequate in women with dense breast composition.

D1Fatty

D2 Fibroglandular

D3 Heteroge-

nously

D4 Extremely

BIRADS ACR; 5th Edition: 2013

In the Western women, 70-75% have D1/D2

Percentage breast density

Relative risk

5-24% 1.7925-49% 2.1150-74% 2.92> 75% 4.64

Mc Cormack VA. Cancer Epidemiol Biomarkers Prev 2006:15:1159.

• Density: masking effect

– Masking effect of breast density leads to an increased percentage of interval breast cancer

– Dense breast may make a woman more likely to be diagnosed with an interval cancer

Breast density and breast cancer risk

Vacek and Geller. Cancer Epidemiol Biomarkers Prev 2004:13:715.Bae MS. Radiology 2014;356:227.

• Density as an independent risk factor

– Density refers to the amount of epithelial and stromal elements of the breast

– The greater amount of epithelial tissue, the greater chance of breast cancer

– Fourfold increase in the risk of breast cancer in women with dense breast

Breast density and breast cancer risk

Microscopic difference between dense and non-dense breast

Breast density in Thai women

Siriraj Experience: Breast densities: 14,770 women

Number %

Fatty breast 287 2.0

Fibrograndular dense 2,357 16.0

Heterogenously dense 10,537 71.3

Extremely dense 1,589 10.7

Total 14,770 100

Korphrapong P et al. Acta Rad 2014;55:903.

Age (yr) Fatty (%) Fibrograndular dense (%)

Heterogenously dense (%)

Extremely dense (%)

<40 4 (0.2) 90 (6.6) 96 (70.9) 300 (22.1)

40-49 37 (0.6) 681(10.2) 4,998 (75.1) 941(14.1)

50-59 106 (2) 1,067 (20.4) 3,754 (71.7) 309 (5.9)

60-69 95 (7.4) 419 (32.8) 725 (56.8) 38 (2.9)

>70 45 (18.4) 100 (40.8) 99 (40.4) 1 (0.4)

Total 287 (2.0) 2,357 (15.9) 10,537 (71.3) 1,589 (10.8)

Siriraj Experience: 14,770 women by age group

• US State of legislation regarding breast density notification started in Connecticut in 2009

Require notification to patients regarding their breast density and informing them that they may benefit from supplemental screening tests

Notification Law (year) Bill Introduced Insurance: cover additional testing

2009: Connecticut2011: Texas2012: California, Virginia2013: Alabama, Maryland,

New York2014: Arizona, Hawaii,

Minnesota, Nevada, New Jersey, North Carolina, Oregon, Pennsylvania, Rhode Island, Tennesse

ColoradoDelawareIllinoisIndianaIowaKentuckyMichiganOhioSouth CarolinaWashington

ConnecticutIndianaIllinoisNew Jersey

Potential supplemental tests

Whole breast ultrasound

Automated whole breast ultrasound

Digital breast tomosynthesis

Contrast-enhanced

mammography

PEM and BSGI

• Hand-held US (HHUS) and automated US (ABUS)

• Improve detection of breast cancer, in particular in non-fatty breast density, range from 0.3 to 6.8 cancers per 1000 exam

• However, increase rate of biopsy and detect more non-cancerous lesions

Findings Screening BC_F/U Diagnose

MMG - mass 22% 26% 40%

MMG - microcal 37% 23% 10%

MMG - mass with microcal 19% 19% 30%

Occult lesions (ultrasound detected)

22% 31% 19%

Breast cancer screening: Siriraj-Thanyarak experience 2001-2005

69,672 examinations1,405 breast cancer lesions from 1,268 patients

Angsusinha T et al.

115 cancers from 14,483 women with non-fatty breast

CANCER (n=115)

Sensitivity (%)MM / MM+US

CDR per1,000MM / MM+US

PPV (%)MM / MM+US

Age group

<40 100 /100 1.4 / 1.4 14.3 / 5.1

40-49 69.6 / 84.8 5.6 / 6.9 29.1 / 14.3

50-59 72.2 / 95.5 6.6 / 8.6 36.4 / 24.6

60-69 88.2 / 94.1 13.5 / 14.4 51.7 / 38.1

>70 83.3 / 100 25 / 30.0 83.3 / 60

Total 74.8 / 91.3 6.5 / 7.9 33.9 / 19.6

Improved 1.4 per 1000

Decreased PPV

Mammography is not enough in detecting small lesions in the women with dense breast, so consider supplemental tests

Automated whole breast ultrasound

Digital breast tomosynthesis

Contrast-enhanced

mammography

Controversies in breast cancer: surgeon’ s concerns

• Nodal status has been designated as the most important prognostic factors

• Nodal status influences adjuvant therapy and treatment outcome

• Sentinel lymph node : the first node or group of node draining in cancer

• Sentinel lymph node biopsy : is the standard of care in early breast cancer management

ITC : less than 2 mm or < 200 cells

Macrometastasis : greater than 2mm.Micrometastasis : 0.2-2 mm

• Isolated tumor cells (ITC) is pathological N0.

• Treatment is as node negative.

Micrometastasis : 0.2-2 mm

Boer M et al. N Engl J Med 2009;361:653.

N=2707

pNmi was inferior to pN0. Therefore, AD should be considered.

Montagna E et al. Breast Cancer Res Treat 2009;118:385.

pNmi was comparable to pN0. Therefore, AD might be an overtreatment.

Langer I et al.. Ann Surg Oncol 2009;16:3366.

931 women with clinically node negative

Positive SLNB : micrometastasis

Both BCS and mastectomy (10%) included

Both randomly to AD or no AD

5 yrs OS : 97.9 % for AD and 98% for no AD (p = 0.35)

5 yrs DFS : 87.3 % for AD and 88.4 % for no AD (p = 0.48)

Golimberti V et al. Lancet Oncol 2013;:297-305.

Isolated tumor cells, and even metastases up to 2 mm (micrometastases) in a single sentinel node, were not

considered to constitute an indication for axillary dissection regardless of the type of breast surgery carried out.

Goldhirsch A et al. Ann Oncol 2011;22:1736.

Axillary dissectionvs

No further surgery

Macrometastasis : >2mm

ACOSOG Z0011

Giuliano AE et al. JAMA 2011;305:569.

Continue from ACOSOG Z0010891 sentinel LN positive (only 1-2 nodes)

115 Cancer Center in the USAll had T1-T2

Undergoing BCS with post-op RT

Giuliano AE et al. JAMA 2011;305:569.

Can axillary RT replace axillary dissection in positive axillary LN following SLNB?

Straver M E et al. JCO 2010;28:731-737

AMAROS Trial2001 to April 20104827 patients35 centers in Europe

Donker et al. Lancet Oncol 2014;1303-10.

Messages from ACOSOG Z0011 and AMAROS trial

Some patients with early breast cancer who had positive sentinel lymph node biopsy may be avoided from axillary dissection, in particular patients who undergone breast

conserving surgery

However, those patients who undergone mastectomy (60% in Siriraj) are still in controversy.

Controversy 3 : Use of IORT following BCS

• Breast conserving therapy (BCT) is the standard of treatment for early breast cancer

• BCT consists of breast conserving surgery (BCS) and whole breast radiation

• Lumpectomy alone without RT showed high recurrent rate

APBI techniques:

Interstitial brachytherapy Balloon catheter brachytherapy

Skowronek J Contemp Brachy 2012;4(3):152-164 http://www.mammosite.com

IORT techniques

Low energy 50 KvIntrabeam

Electron Mobetron

IORT : local recur = 3.3 %, 95% CI = 2.3-5.11WBRT : local recur = 1.3%, 95%CI = 0.7-2.5

Difference =2.0%

IORT : local recur = 4.4 %, 95% CI = 2.7-6.1WBRT : local recur = 0.4 %, 95%CI = 0.0-1.0

No difference in mortality

Subsequent analysis identified factors associated with LR in IORT group

On muliti-variated analysis, factors associated with LR were

Factor Hazard ratio 95% CI

Size > 2 cm 2.24 1.03-4.87

Node positive > 4 2.61 0.91-7.50

Poorly diff 2.18 1.00-4.79

Triple negative 2.4 0.94-6.1

The logical conclusion is that intraoperative radiation therapy with

electrons should be restricted to suitable patients, once characteristics defining

suitability have been defined.

Boost (9 Gy) Single dose (21 Gy)Invasive breast cancer and age less than 50 year

Invasive ductal carcinoma and favorable histology

or Age ≥ 55 yearInvasive breast cancer and tumor size > 2 cm from imaging

Tumor ≤ 2 cm from imaging or previous surgery

or Single malignant lesion

Invasive breast cancer and angiolymphatic invasion evidenced in core needle biopsy

Estrogen receptor positive

No angiolymphatic invasion or extensive intraductal component from previous core biopsyNode negative

1. Wide excision done.

2. Mobilize breast tissue at least 2 cm around the cavity and do purse-string suture.

3. Move Mobetron in and do docking.

Characteristics Boost group (N=23) Single group (N=79) Overall (N=102)

Age (yr) : mean 51.2 (33-78) 64.8 (54-90) 61.7 (33-90)

Tumor size (cm) : mean

1.6 (0.5-4.0) 1.3 (0.3-3.2) 1.4 (0.3-4.0)

Histology

- Invasive ductal CA

21 (100%) 72 (91.0%) 93 (91.1%)

- Mucinous CA 0 2 (2.5%) 2 (2.0%)

- Invasive papillary CA

0 5 (6.5%) 5 (4.9%)

ER positive 21 (91.3%) 79 (100%) 100 (98%)

Nodal status

- N0 15 (65.3%) 76(96.2 %) 91 (89.2%)

- N1 7 (30.4%) 3 (3.8 %) 10 (9.8%)

- N2 1 (4.3%) 0 1 (1.0%)

IORT: Result from Siriraj Hospital

Characteristics Boost group (N=23) Single group (N=79) Overall (N=102)

Age (yr) : mean 51.2 (33-78) 64.8 (54-90) 61.7 (33-90)

Tumor size (cm) : mean

1.6 (0.5-4.0) 1.3 (0.3-3.2) 1.4 (0.3-4.0)

Histology

- Invasive ductal CA

21 (100%) 72 (91.0%) 93 (91.1%)

- Mucinous CA 0 2 (2.5%) 2 (2.0%)

- Invasive papillary CA

0 5 (6.5%) 5 (4.9%)

ER positive 21 (91.3%) 79 (100%) 100 (98%)

Nodal status

- N0 15 (65.3%) 76(96.2 %) 91 (89.2%)

- N1 7 (30.4%) 3 (3.8 %) 10 (9.8%)

- N2 1 (4.3%) 0 1 (1.0%)

Characteristics Boost group (N=23)

Single group (N=79) Overall (N=102)

Median follow up time (days)

1258.5 (401-1523) 634.43 (100-1458) 946.45 (100-1523)

AXLD 10 (43.5%) 0 10 (9.8%)

Op time (mins) 125.9 (72-235) 126.4 (80-194) 126.3 (80-235)

Positive margin 0 2 (4.5%) 2 (3%)

Ipsilat recurrence 1 (4.3%) 1 (1.3%)(axillary) 2 (1.9%)

Contralat recurrence 1 (4.3%) 2 (2.5%) 3 (2.9%)

Systemic recurrence 2 (8.7%) 0 2 (1.9%)

BCA related death 2 (8.7%) 0 2 (1.9%)

Non-BCA death 0 1 (1.3%) 1 (1.0%)

Total save of ERT procedures

115 1975 2090

Controversy 3

IORT following breast conserving surgery has shown higher ipsilateral recurrence than conventional whole breast

irradiation

However, in some selected patients, the non-inferior result might be demonstrated.

Controversies in Surgical Approach to Breast Cancer

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