Dr. NIPPAKNGAI

1. Margin of Breast Conservative Surgery:
How much is enough?
Pathology IC: Nip Pak Ngai
Tutor: Dr. Ng Wai Lon

2. Background
• Breast cancer is the most common malignant tumor in women
worldwide with 2.26 million new cases in 2020.
• In Macau, breast cancer is the most common cancer (24%) among
females.
Łukasiewicz S, et al. Cancers (Basel). 2021 Aug 25;13(17):4287.
Annual report of Macau cancer registry 2020
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3. Background
• Treatments
• Chemotherapy
• Target therapy
• Hormone therapy
• Radiotherapy
• Surgery
• Mastectomy
• BCS (Breast conservative
surgery)
Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341
Guideline on Margins for Breast-Conserving Surgery With Whole-Breast Irradiation in Ductal Carcinoma In Situ.
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• Factors associating LR, prognosis
• Age
• Tumor size and grade
• Histologic subtype
• Biologic subtype
• ER
• PR
• HER
• Surgical margin

4. Background
• Approximately 25% of patients with invasive carcinoma and
one-third of those with DCIS undergo re-excision. About
half of the re-excisions done in patients with negative
margins (defined as no ink on tumor)
• There has been considerable controversy regarding the
optimal negative margin width to minimize local recurrence
(LR) in patients undergoing breast conservative surgery
(BCS).
• Here we review the available data on margin status for
invasive breast cancer and DCIS.
Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341.
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5. Margin Assessment in Pathology
• The negative margin width reported by the pathologist is dependent on
multiple factors:
o number of sections examined
o technique of margin assessment (perpendicular, shaved, cavity margins)
o use of specimen compression devices
Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341.
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6. Specimen handling in
Pathology
• Measure
• Orientate
• Marking
• Slicing
• Photo
• Sampling
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Dept. of Pathology(QMH, HK) - Manual of Ancillary Studies in Anatomic Pathology 5th

7. Margin Width and LR Risk in
DCIS
Treated with Excision Alone
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8. Margin Width and LR Risk in DCIS Treated with
Excision Alone
• Margin width is one of the factors influence the risk of LR following
BCS for DCIS.
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Van Zee KJ, et al. Ann Surg. 2015 Oct;262(4):623-31.

9. Margin Width and LR Risk in DCIS Treated with
Excision Alone
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Solin LJ, et al. J Clin Oncol. 2015 Nov 20;33(33):3938-44.

10. Margin Width and LR Risk in DCIS Treated with
Excision Alone
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Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341.
the heterogeneity of the evidence between the above-reported studies
did not allow for a definitive recommendation for uniform margin
widths in patients without RT

11. 11
Margin Width and LR Risk in
DCIS
(Treated with Excision and RT)

12. Margin Width and LR Risk in DCIS Treated with
Excision and RT
• DCIS has a 10-year mortality under 1% after BCS, but optimising local control
is important, LR events are associated increased risk of breast cancer-specific
mortality.
• The rate of ipsilateral breast tumor recurrence decreased significantly with the
addition of RT.
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McCormick B, et al. J Clin Oncol. 2015 Mar 1;33(7):709-15.

13. Margin Width and LR Risk in DCIS Treated with
Excision and RT
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• 2 mm margin minimizes the risk of LR compared with smaller
negative margins, more widely clear margins do not further reduce
the risk of LR
Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341.

14. Margin Width and LR Risk in
Invasive Cancer
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15. Margin Width and LR Risk in Invasive Cancer
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• Negative margin reduces the risk of LR; however, increasing the size of a negative
margin is not significantly associated with improvement in local control.
Houssami N, et al. Ann Surg Oncol. 2014 Mar;21(3):717-30.

16. Margin Width and LR Risk in Invasive Cancer
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• Negative margin can be used even in the high-risk TNBC cohort
Pilewskie M, et al. Ann Surg Oncol. 2014 Apr;21(4):1209-14.

17. 17
Margin Width and LR Risk in Invasive Cancer:
Recent study
Bundred JR, et al. BMJ. 2022 Sep 21;378:e070346.
Inadequate margin widths may result in higher risks of distant recurrence and
breast cancer mortality, as well as increased local recurrence.
A margin of no tumour on ink is inadequate and a minimum tumour-free distance
of 1 mm is recommended from the margin for either invasive disease or ductal
carcinoma in situ to ensure optimum oncological outcomes.

18. ASCO recommendations
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DCIS Treatment with
excision alone
Treatment with excision alone, regardless of margin width, is
associated with substantially higher rates of IBTR(ipsilateral
tumor recurrence) than treatment with excision and RT, even in
predefined low-risk patients. The optimal margin width for
treatment with excision alone is unknown, but should be at
least 2 mm. Some evidence suggests lower rates of IBTR with
margin widths wider than 2 mm.
Treatment with
excision and RT
Margins of at least 2 mm are associated with a reduced risk of
IBTR(ipsilateral tumor recurrence) relative to narrower negative
margin widths in patients receiving WBRT. The routine practice
of obtaining negative margin widths wider than 2 mm is not
supported by the evidence.
Invasive breast cancer the use of no ink on tumor [no cancer cells adjacent to any
inked edge/surface of the specimen] as the standard for an
adequate margin in invasive cancer in the era of multidisciplinary
therapy is associated with low rates of IBTR and has the
potential to decrease re-excision rates, improve cosmetic
outcomes, and decrease healthcare costs
Monica Morrow, et al. Journal of Clinical Oncology 2016 34:33, 4040-4046.
Thomas A. Buchholz, et al. Journal of Clinical Oncology 2014 32:14, 1502-1506.

19. Special cases
• DCIS with microinvasive: Behavior of microinvasive
carcinoma is more similar to DCIS than invasive cancer,
and the use of systemic therapy is more similar to that seen
in DCIS.
• Invasive cancer with associated DCIS, should be
managed according to the invasive guideline. The biology
of the invasive cancer is the primary determinant of
outcome and the majority of patients will receive systemic
therapy.
Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341.
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20. Special cases
• DCIS with Margin < 2mm, decision to perform a re-excision
should be individualized based upon multiple factors
• volume of disease near a margin
• results of a post-excision mammogram
• cosmetic impact of re-excision
• patient age
• tumor size and grade
• life expectancy
• patient tolerance of risk
• MDT discussion for further plan of treatment
Pilewskie M, Morrow M. Cancer. 2018 Apr 1;124(7):1335-1341.
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21. Conclusions
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 In the modern era of multimodality therapy for invasive and in situ
breast carcinoma, margin status is one of a number of factors
impacting LR risk.
 In patients with DCIS receiving RT, a margin of 2mm minimizes
local recurrence, larger margins do not provide additional benefit.
 For invasive breast cancer, ASCO suggest obtaining a negative
margin, defined as ‘no ink on tumor’, and no additional benefit for
more widely clear margins.
 In special cases, different treatment plan including re-excision
based on multiple factor, an MDT discussion is recommended.
 More studies are needed to explore and validate the definitive
margin widths in the future.

22. The End
Thank you very much for your attention!

23. • Łukasiewicz S, Czeczelewski M, Forma A, Baj J, Sitarz R, Stanisławek A. Breast Cancer-Epidemiology, Risk Factors,
Classification, Prognostic Markers, and Current Treatment Strategies-An Updated Review. Cancers (Basel).
2021;13(17):4287. Published 2021 Aug 25. doi:10.3390/cancers13174287
• Morrow M, Van Zee KJ, Solin LJ, et al. Society of Surgical Oncology-American Society for Radiation Oncology-American
Society of Clinical Oncology Consensus Guideline on Margins for Breast-Conserving Surgery With Whole-Breast
Irradiation in Ductal Carcinoma In Situ. J Clin Oncol. 2016;34(33):4040-4046. doi:10.1200/JCO.2016.68.3573
• Buchholz TA, Somerfield MR, Griggs JJ, et al. Margins for breast-conserving surgery with whole-breast irradiation in
stage I and II invasive breast cancer: American Society of Clinical Oncology endorsement of the Society of Surgical
Oncology/American Society for Radiation Oncology consensus guideline. J Clin Oncol. 2014;32(14):1502-1506.
doi:10.1200/JCO.2014.55.1572
• Pilewskie M, Morrow M. Margins in breast cancer: How much is enough?. Cancer. 2018;124(7):1335-1341.
doi:10.1002/cncr.31221
• Pilewskie M, Ho A, Orell E, et al. Effect of margin width on local recurrence in triple-negative breast cancer patients
treated with breast-conserving therapy. Ann Surg Oncol. 2014;21(4):1209-1214. doi:10.1245/s10434-013-3416-5
• Van Zee KJ, Subhedar P, Olcese C, Patil S, Morrow M. Relationship Between Margin Width and Recurrence of Ductal
Carcinoma In Situ: Analysis of 2996 Women Treated With Breast-conserving Surgery for 30 Years. Ann Surg.
2015;262(4):623-631. doi:10.1097/SLA.0000000000001454
• Bundred JR, Michael S, Stuart B, et al. Margin status and survival outcomes after breast cancer conservation surgery:
prospectively registered systematic review and meta-analysis. BMJ. 2022;378:e070346. Published 2022 Sep 21.
doi:10.1136/bmj-2022-070346
• Houssami N, Macaskill P, Marinovich ML, Morrow M. The association of surgical margins and local recurrence in women
with early-stage invasive breast cancer treated with breast-conserving therapy: a meta-analysis. Ann Surg Oncol.
2014;21(3):717-730. doi:10.1245/s10434-014-3480-5
• Dept. of Pathology(QMH, HK) - Manual of Ancillary Studies in Anatomic Pathology 5th Ed.
• Annual report of Macau cancer registry 2020
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References

24. • DCIS within one quadrant may be extensive, with
46% of lesions measuring >3cm in one study. 13
Faverly and colleagues examined the growth
pattern of DCIS and found that while 90% of poorly
differentiated lesions grew continuously, 70% of
well-differentiated lesions had a multifocal, skip
pattern, with 82% of skip lesions measuring
between 0mm to 5mm, and only 8% having skip
lesions >10mm. 45 These studies suggest that that
a small negative margin may lie within a skip lesion
and may be associated with a substantial residual
tumor burden.
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