Disclosures Nothing relevant to report. 1 Defining the Problem 5% - - PDF document

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CON: Removal of the Breast Primary in Patients with Metastatic Breast Cancer

Amelia B. Zelnak, MD, MSc

Assistant Professor of Hematology and Medical Oncology Winship Cancer Institute Emory University School of Medicine

Disclosures

• Nothing relevant to report.

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Defining the Problem

• 5% of women with breast cancer present with

metastatic disease

– Staging scans often performed after initial surgery

• Current approach: treat with systemic therapy

and offer surgery if needed for palliation

• Does local therapy improve survival?
• What constitutes adequate local therapy?

– Breast‐conserving surgery vs. mastectomy – Role of radiation

• When is the optimal time for local therapy

Rationale for Local Therapy

PRO

– Primary tumor is source of reseeding distant sites and therefore should be removed

CON

– Once patient develops distant metastases, local therapy offers no survival advantage

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Proof of Principle: The kidney

SWOG 8949 (N=241) EORTC 30947 (N=75)

IFN‐Alfa2b (months) Nephrectomy + IFN‐Alfa2b (months) Median Survival 8.1 11.1 Performance Status 0 11.7 17.4 Performance Status 1 4.8 6.9 Lung only 10.3 14.3 Other 6.3 4.2 Flanigan et al, N Engl J Med 2001 Mickisch et al, Lancet 2001 IFN‐Alfa2b (months) Nephrecto my + IFN‐ Alfa2b (months) Median Survival 7 17

Retrospective Study: Khan et al.

• National Cancer Database: 16,023 patients

presented with metastatic breast cancer between 1990‐1993

– 6861 (42.8%) did not have surgery – 9162 (57.2%) underwent either partial or total mastectomy – 10,160 with complete information included in the analysis

• 5806 (36.2%) received radiation therapy,

unknown if this was local or to metastatic site

Khan et al, Surgery 2002

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Khan et al.

Surgical Therapy 3 Year Survival Mean Survival (months) Overall 24.9% None 17.3% 19.3 Partial Mastectomy 27.7% 26.9 Total Mastectomy 31.8% 31.9

• No. Patients

Hazard Ratio 95% CI No operation 4735 Negative Margins 3099 0.612 0.581‐0.646 Positive Margins 2326 0.751 0.710‐0.793 Metastatic Burden 1 site 6490 2 sites 2352 1.25 1.185‐1.319 3 sites 1318 1.523 1.424‐1.629 Type of Metastasis Visceral 3944 Soft tissue 6216 0.747 0.713‐0.782

Limitations: Khan et al.

• Patients with 1 metastatic site were more likely to undergo

surgical resection

• Patients with bone/soft‐tissue metastases (61.7%) were more

likely to undergo surgery vs. patients with visceral metastases (52.7%)

• Data regarding receptor status is unknown.
• Unknown whether patients were diagnosed with metastatic

disease after surgery or before Does local therapy really make a difference or are we simply identifying metastatic breast cancer patients with better prognosis?

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Retrospective Study: Rapiti et al.

• Geneva Cancer Registry: 300 metastatic breast

cancer patients diagnosed between 1977‐1996

• 76% presented with symptoms of primary tumor
• r metastatic sites
• Potential Bias among Surgery Patients

– Mean age of women of patients undergoing surgery was younger (61.8 vs. 71.6 years) – lower T and N stage – Only 1 metastatic site (61% vs. 41%) – Visceral metastases were less common (43% vs. 58%)

Rapiti et al., J Clin Oncol 2006

Rapiti et al.

Surgery No. Patients Hazard Ratio 95% CI No operation 173 Negative Margins 61 0.5 0.3‐0.7 Positive Margins 33 0.8 0.5‐1.1 Unknown Margins 33 0.8 0.6‐1.3

Is local therapy responsible for the difference? Were patients with positive margins too sick for additional surgery? Did their tumors have poor prognostic features?

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• Population‐based cohort study

using SEER database from 1988‐2003 of 9734 patients with Stage IV breast cancer

• 4578 (47%) underwent breast

surgery

– 1844 (40.3%) had partial mastectomies – 2485 (54.3%) had mastectomies

• 5156 (53%) did not have breast

surgery

• Surgery group was younger

(medain age of 62 vs 66), smaller tumors, ER/PR‐positive

Retrospective Study of SEER Database

Gnerlich et al., Ann Surg Oncol 2007

Median Overall Survival 36 vs 21 months (P < 0.001)

Impact of Staging and Patient Selection

• Retrospective Analysis of

147 patients who presented with stage IV breast cancer at Dana‐ Farber between 1998 and 2005

• 61 (41%) underwent breast

surgery

• Adjusted for age, number
• f metastatic sites, used of

chemotherapy, endocrine therapy, receptor status

Bafford et al. Breast Cancer Res Treat 2009

Median Overall Survival 4.1 vs 2.4 years, favoring surgery (P = 0.003)

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Impact of Staging and Patient Selection

Bafford et al. Breast Cancer Res Treat 2009

• 61 (41%) underwent breast

surgery

– 25 had surgery after diagnosis of stage IV disease – 31 had surgery before diagnosis of stage IV disease

• Median Survival varied

significantly based on timing of stage IV diagnosis

– Post surgery: 4.05 years – Pre surgery: 2.4 years No difference seen in survival between presurgery and no surgery groups

Retrospective Study: Babiero et al.

• MDACC: 224 patients presented with stage IV

disease and intact primary tumor between 1997 and 2002.

• Median age 52
• 142 (63%) did not have surgery
• 82 (37%) underwent surgery

– 39 (48%) had breast‐conserving surgery – 43 (52%) had mastectomy

• Surgery group was younger, had fewer sites of

metastatic disease, less nodal involvement; more likely Her2‐positive

Babiero et al., Ann Surg Oncol 2006

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Babiero et al.

Babiero et al., Ann Surg Oncol 2006

Overall Survival Progression‐Free Survival

Update on MDACC Series

• Longer follow‐up (74.2 vs. 32.1 months)
• Excluded 16 patients from prior analysis

N=208

• 74 (35.5%) underwent breast surgery

– 33 Breast‐conserving surgery; 41 mastectomy – 32% received local RT: 9 after BCS, 15 after mastectomy

• 44 (59.5%) had proven metastatic disease

presurgery; 30 diagnosed within 3 months of surgery

Lang et al. Ann Surg Oncol 2013

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Update on MDACC Series

Lang et al. Ann Surg Oncol 2013

Update on MDACC Series

Lang et al. Ann Surg Oncol 2013

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ECOG‐ACRIN 2108

Planned Accrual = 368 Registration may occur at time of diagnosis up to 30th week of treatment Randomization must occur between week 16 to 32