All of the findings indicate that inadequate margin widths result in higher risks of distant recurrence and breast cancer mortality, as well as increased total recurrence.
New research has found that involved or close pathological margins after breast conserving surgery for early-stage, invasive breast cancer are associated with increased risk of distant or local recurrence. Based on the findings, investigators recommend that surgeons aim to achieve a minimum clear margin of at least 1 mm.
Involved or close pathological margins after breast conserving surgery for early invasive breast cancer are known to be associated with an increased risk of local recurrence and patients who develop local recurrence have an increased risk of developing distant recurrence and death from breast cancer. The researchers noted that in 2014, the American Society of Clinical Oncology (ASCO) said that tumors not touching the ink at the edge of the specimen is acceptable to prevent local recurrence.
Despite this knowledge, the effect of margin involvement on distant recurrence or mortality is relatively unknown. A previous study of young women aged 40 years or younger with early-stage invasive breast cancer reported that in those undergoing breast conserving surgery, 21% had margins of 1 mm or less. This was associated with a 13.4% higher rate of distant recurrence and an 11.1% decrease in overall survival (OS) at 5 years compared with women who had margins of more than 1 mm.
To further understand the incidence of tumor on ink and close margins after breast conserving surgery, as well as any association between margin involvement with subsequent distant recurrence and OS, researchers performed a systematic review and meta-analysis.
Eligible studies reported on patients undergoing breast conserving surgery for stages 1 through 3 breast cancer, allowed an estimation of outcomes in relation to margin status, and followed up with patients for a minimum of 60 months. Patients with ductal carcinoma in situ only or who were treated with neoadjuvant chemotherapy or mastectomy were excluded. Where applicable, margins were categorized as tumor on ink (involved), close margins (no tumor on ink by less than 2 mm), and negative margins (2 mm or more).
Researchers identified 68 studies conducted between 1980 and the end of 2021, comprising of 112,140 patients with breast cancer. Across all studies, 9.4% of patients had involved margins and 17.8% had tumor on ink or a close margin.
The rate of distant recurrence was 25.4% in patients with tumor on ink, 8.4% in patients with tumor on ink or close, and 7.4% in patients with negative margins. Compared with negative margins, tumor on ink margins were associated with increased distant recurrence and local recurrence, whereas close margins were associated with increased distant recurrence and local recurrence, after adjusting for receipt of adjuvant chemotherapy or radiotherapy.
Based on these findings, the authors said they do not support the overall conclusion expressed in the 2014 ASCO guidelines. Most international guidelines advise a threshold margin to reduce local recurrence, but the study shows that margin proximity is associated with increased recurrence, so the chosen margin width is important and should minimize distant recurrence.
The interplay between positive margins and chemotherapy on distant recurrence was analyzed both as a meta-regression and as a subgroup of studies, which had adjusted for use of chemotherapy. Within both of these analyses, the association between positive or close margins and adverse oncological outcomes was not attenuated by chemotherapy. Clear margins were associated with reduced distant recurrence by an absolute value of 5% across all studies, which the researchers said is a level of benefit for which chemotherapy is commonly offered to patients as adjuvant therapy.
Taken together, the investigators said that all of the findings indicate that inadequate margin widths result in higher risks of distant recurrence and breast cancer mortality, as well as increased total recurrence. A margin of no tumor on ink is inadequate and the investigators recommend a minimum tumor-free distance of 1 mm from the margin for either invasive disease or ductal carcinoma in situ in order to ensure optimal outcomes.
Bundred JR, Michael S, Stuart B, Cutress RI, et al. Margin status and survival outcomes after breast cancer conservation surgery: prospectively registered systematic review and meta-analysis. The BMJ; September 21, 2022. Accessed September 23, 2022. https://www.bmj.com/content/378/bmj-2022-070346