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Monica Morrow MD Chief, Breast Surgery Service Anne Burnett Windfohr Chair of Clinical Oncology Memorial Sloan-Kettering Cancer Center PowerPoint PPT Presentation


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18 th Annual Perspectives in Breast Cancer New York, NY. Memorial Sloan-Kettering Cancer Center 1275 York Avenue, New York, NY 10065. 18 August 2012. Treatment Decision Making for DCIS. Monica Morrow MD Chief, Breast Surgery Service Anne Burnett Windfohr Chair of Clinical Oncology

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Monica Morrow MD Chief, Breast Surgery Service Anne Burnett Windfohr Chair of Clinical Oncology Memorial Sloan-Kettering Cancer Center

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Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

18th Annual Perspectives in Breast Cancer

New York, NY

Memorial Sloan-Kettering Cancer Center

1275 York Avenue, New York, NY 10065

18 August 2012

Treatment Decision Making for DCIS

Monica Morrow MD

Chief, Breast Surgery Service

Anne Burnett Windfohr Chair of Clinical Oncology

Memorial Sloan-Kettering Cancer Center


Controversies in dcis management

Controversies in DCIS Management

  • Is nipple sparing mastectomy appropriate?

  • Is RT necessary for all DCIS?

  • When is SN biopsy indicated?

  • What about endocrine rx?


Mastectomy in dcis

Mastectomy in DCIS

  • Indicated when DCIS is too extensive to be encompassed with a cosmetic resection.

  • Outcome

    • Metaanalysis 21 studies, 1574 patients

    • Local recurrence 1.4% (0.7-2.1%)

    • Skin sparing mastectomy n = 223

    • Local recurrence 3.1%

Boyages J, Cancer 1999;85:616

Carlson G, JACS 2007;204:1074


What about nipple sparing mastectomy

What About Nipple Sparing Mastectomy?

  • Concerns

  • NSM leaves behind ductal tissue + breast tissue in order to preserve blood supply.

  • Occult nipple involvement present in 6-31% of cancers.

  • Most studies of NSM are in invasive cancer.


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

10/26/2011


Clinical outcomes nsm european institute of oncology 3 02 12 07

Clinical Outcomes NSMEuropean Institute of Oncology 3/02-12/07

  • Median f/u: 50 months

  • All patients received 16 Gy to NAC

  • CAUTION: At 20 mo f/u, no NAC recurrences, 1.4% LR

Petit JY, Ann Oncol 2012;23:2053-8

Petit JY, Br Ca Res Treat 2009;117:333


Nsm in dcis

NSM in DCIS

  • Increased risk of LR due to retained breast tissue and poor exposure.

  • Contraindicated in patients with extensive DCIS necessitating mastectomy, localized DCIS in subareolar space.


What do i really think about nsm

What do I really think about NSM?

  • It’s a great operation for a woman

  • who doesn’t actually need a mastectomy.


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Is RT Necessary for All DCIS?


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Randomized Trials of Excision ± RT

in DCIS


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Metaanalysis Trials of Excision ± RT

in DCIS

n = 3729

10 yr IBTR

EBCTCG JNCI Monograph 2010;41:162


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Metaanalysis Trials of Excision ± RT

in DCIS

10 yr Survival Outcomes

EBCTCG JNCI Monograph 2010;41:162


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Conclusions of Randomized Trials

  • RT reduces the risk of LR by 50%.

  • Patient subsets NOT benefitting from RT have not been identified.


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Academic U.S. Physicians

Recommending RT For DCIS

Ceilley E, Cancer 2004;101:1958


Concerns regarding randomized trials

Concerns Regarding Randomized Trials

Detailed tissue processing/method of pathology evaluation not specified.

Post-excision mammography not mandated.

Impact of margin width on RT benefit not assessed.


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Does wide excision + detailed pathology exam

result in local control equivalent to excision + RT?


Local recurrence margins 10 mm

Local Recurrence: Margins ≥ 10 mm

Silverstein M, NEJM 1999;340:1455


E5194 excision alone tamoxifen for dcis eligibility

E5194: Excision Alone ± Tamoxifen for DCIS Eligibility

DCIS ≥ 3mm in size

Minimum margin width ≥ 3mm

Specimen completely embedded, sequentially sectioned

Post-excision mammogram free of calcification

Hughes L, J Clin Oncol 2009;27:5319


Patient characteristics e5194

Patient Characteristics: E5194

Hughes L, J Clin Oncol 2009;27:5319


Intergroup trial of excision alone

Intergroup Trial of Excision Alone

Mean f/u 6.3 years

Hughes L, J Clin Oncol 2009;27:5319


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Local Failure According to Pathology

After Lumpectomy and Radiation

Solin L, J Clin Oncol 1996;14:754


Effect of margin width no rt

Effect of Margin Width – No RT

Hughes L, J Clin Oncol 2009;27:5319


Rtog 9084 rt vs observation for good risk dcis

RTOG 9084: RT vs Observation for “Good Risk” DCIS

Mammographic or incidental DCIS

Low or intermediate grade

Size (mammographic) ≤ 2.5 cm

Margins ≥ 3 mm

Eligibility

McCormick B, ASCO 2012


Rtog 9084 schema

RTOG 9084 Schema

Stratify

Age

< 50

≥ 50

Margins

Negative re-excision

3-9 mm

≥ 10 mm

Size

≤ 1 cm

> 1 cm-2.5 cm

Grade

Low

Intermediate

Tamoxifen

No

Yes

RANDOMIZE

Observation

RT

No Boost


Patient characteristics rtog 9084

Patient Characteristics: RTOG 9084

McCormick B, ASCO 2012


Local failure ipsilateral breast

Local Failure Ipsilateral Breast

5-Years Rates:

3.2%

0.4%


Local recurrence after excision rt in good prognosis dcis

Local Recurrence After Excision +/- RT in Good Prognosis DCIS

5 yr LR

Hughes L, J Clin Oncol 2009;27:5319

McCormick B, ASCO 2012


Conclusions e5194 rtog 9084

Conclusions E5194 + RTOG 9084

Rates of LR after excision alone differed significantly among 2 populations with “favorable” DCIS selected with standard histopathologic criteria.

Benefit for RT is present even in this good-risk subset.


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

A QUANTITATIVE MULTIGENE RT-PCR ASSAY FOR PREDICTING RECURRENCE RISK AFTER SURGICAL EXCISION ALONE WITHOUT IRRADIATION FOR DUCTAL CARCINOMA IN SITU (DCIS): A PROSPECTIVE VALIDATION STUDY OF THE DCIS SCORE FROM ECOG E5194 Solin LJ, Gray R, Baehner FL, Butler S, Badve S, Yoshizawa C, Shak S, Hughes L, Sledge G, Davidson N, Perez EA, Ingle J, Sparano J, Wood W Eastern Cooperative Oncology Group (ECOG)North Central Cancer Treatment Group (NCCTG)Genomic Health, Inc (GHI)2011 San Antonio Breast Cancer Symposium


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

DCIS Recurrence Score:

Unanswered Questions

  • Do patients in the low-risk group benefit from RT? Is it predictive as well as prognostic?

  • Does it apply to the wider population of women with DCIS?

  • Validation needed


Sentinel node biopsy in dcis

Sentinel Node Biopsy in DCIS

  • DCIS lacks the ability to metastasize.

  • Rationale for axillary surgery is risk of unsampled invasive cancer.

  • ~15% risk of invasion after core bx diagnosis of DCIS.


Risk of axillary recurrence in dcis

Risk of Axillary Recurrence in DCIS

NSABPB17:7 of 623 pts with axillary recurrence

1 s/p axillary dissection

3 with invasive IBTR

3 of 620 with DCIS at 15 yrs

NSABPB24:6 of 1799 pts at 11.6 yrs

1 with undiagnosed microinvasion

Julian, Ann Surg Oncol 2006


Risk of axillary recurrence in dcis1

Risk of Axillary Recurrence in DCIS

Julian, Ann Surg Oncol 2006


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

When Should Axillary Nodes

Be Examined in DCIS?

  • • Microinvasive carcinoma

  • Metastases in 3% - 20% of cases.

  • • DCIS treated by mastectomy.

  • Opportunity lost if invasion found.

  • • Done as a second procedure if invasion found after lumpectomy.

  • Prior biopsy does not interfere with mapping.


Benefit of tamoxifen in er dcis

Benefit of Tamoxifen in ER+ DCIS

NSABP B24 n = 732

Allred DC, J Clin Oncol 2012;30:1268-73


Monica morrow md chief breast surgery service anne burnett windfohr chair of clinical oncology memorial sloan kettering

Other Therapies in DCIS

  • • Exemestane

  • MAP 3 — 112 of 4560 had DCIS

  • HR 0.47 (95% CI, 0.27-0.79)

  • No subset analysis

  • Data on other AIs coming from NSABP B35, IBIS II

  • Raloxifene

  • Equivalent to tamoxifen in STAR overall, better side-effect profile

  • DCIS analysis RR 1.46 (95% CI, 0.90-2.41)

Goss PE, NEJM 2011;364:2381-91

Vogel VJ, JNCI Monogr 2010:181-6


Conclusions endocrine rx

Conclusions: Endocrine Rx

  • Endocrine therapy is an option for women desiring to minimize future breast cancer events.

  • Most favorable risk-benefit ratio is in premenopausal women with 2 breasts.


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