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Positive margins after mastectomy in patients with invasive lobular carcinoma of the breast: Incidence and management strategies

Open AccessPublished:June 09, 2021DOI:https://doi.org/10.1016/j.amjsurg.2021.05.021

      Highlights

      • The positive margin rate after mastectomy for invasive lobular carcinoma is unknown.
      • In patients undergoing mastectomy for lobular breast cancer, positive margins occurred in 18.7% of those with T3 tumors.
      • Additional local therapy for positive margins was associated with significantly improved outcomes over only systemic therapy.

      Abstract

      Background

      Surgical treatment of invasive lobular carcinoma (ILC) is challenging due to its diffuse growth pattern, and the positive margin rate after mastectomy is poorly described.

      Methods

      We retrospectively determined the positive margin rate in those with stage I-III ILC undergoing mastectomy. We evaluated the relationship between management strategy and recurrence free survival (RFS).

      Results

      In 357 patients, the positive margin rate was 10.6% overall and 18.7% in those with T3 tumors. Having a positive margin was associated with significantly shorter RFS on multivariate analysis (p = 0.01). Undergoing additional local treatment (radiation or re-excision) for a positive margin was significantly associated with improved RFS (p = 0.004). Older women with positive margins were significantly less likely to undergo additional local therapy.

      Conclusions

      Even mastectomy fails to clear margins in a high proportion of patients with large ILC tumors, a finding which may warrant testing neoadjuvant strategies even prior to planned mastectomy.

      Keywords

      Introduction

      Invasive lobular carcinoma (ILC) is the second most common type of breast cancer, comprising 10–15% of all cases.
      • Mamtani A.
      • Zabor E.C.
      • Rosenberger L.H.
      • Stempel M.
      • Gemignani M.L.
      • Morrow M.
      Was reexcision less frequent for patients with lobular breast cancer after publication of the SSO-ASTRO margin guidelines?.
      ILC is characterized by the lack of the cell adhesion protein E-cadherin and grows in a more diffuse and infiltrating pattern than its invasive ductal counterpart. Due to the nature of its growth pattern, a major challenge in the management of ILC is obtaining clear margins at the time of surgical resection. Many studies show that 30–60% of patients with ILC have positive margins after breast conserving surgery.
      • Piper M.L.
      • Wong J.
      • Fahrner-Scott K.
      • et al.
      Success rates of re-excision after positive margins for invasive lobular carcinoma of the breast.
      Because of this, some investigators have suggested that patients with ILC should preferentially undergo mastectomy instead of breast conservation, and indeed mastectomy rates are higher in those with ILC than in patients with invasive ductal carcinoma.
      • Sledge G.
      • Chagpar A.
      • Perou C.
      Collective wisdom: lobular carcinoma of the breast.
      However, positive margins can still occur even after mastectomy, and the magnitude of this risk is not described in ILC. When positive margins do occur after mastectomy, the optimal management strategy (e.g. no further local therapy, re-excision, radiotherapy) is unknown.
      We therefore sought to determine the incidence of positive margins after mastectomy for patients with stage I-III ILC and the outcomes associated with subsequent management strategies (additional local therapy versus none). Additionally, we evaluated factors associated with having a positive margin after mastectomy and factors associated with undergoing additional local therapy.

      Methods

      With approval from our Institutional Review Board, we queried a prospectively maintained institutional database and identified 700 cases of ILC who underwent surgical treatment at our institution. All patients with stage I-III disease who underwent mastectomy as their definitive operation were included. We collected data on patient demographics, operative details for the initial and any subsequent operations, tumor characteristics, margin status, positive margin location when available, adjuvant therapy, presence of local or distant recurrence, and follow-up time. The primary outcome was positive mastectomy margin rate, and the secondary outcome was recurrence free survival (RFS) estimates, defined as the absence of both local and distant recurrence. Mastectomy type was defined as total skin-sparing mastectomy (TSSM) if the entire skin envelope, including the nipple-areola skin, was preserved and immediate reconstruction performed, skin-sparing mastectomy (SSM) if the nipple-areola complex skin was excised and immediate reconstruction performed, and simple mastectomy (SM) if the nipple areola complex skin was excised and no immediate reconstruction performed.
      Positive margins were defined as ink on tumor based on guidelines established by the Society of Surgical Oncology (SSO) and The American Society for Radiation Oncology (ASTRO).
      • Buchholz T.A.
      • Somerfield M.R.
      • Griggs J.J.
      • 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.
      Mastectomy specimens were evaluated via our institutional protocol, including use of three color inking, slicing in 0.5–1 cm slices, and routine histologic analysis with hematoxylin-eosin staining; additional staining or levels were performed selectively. Margin status at the time of mastectomy was used to designate positive versus negative margins, and status of any subsequent re-excision was described separately. Pathologic staging was assigned based on the American Joint Committee on Cancer 7th edition. The data were analyzed using Stata 14.2 using the chi squared test to compare categorical variables, t-tests for continuous data, the log rank test for survival analysis, and a Cox proportional hazards model for multivariate analysis. Two-tailed p values < 0.05 were considered significant.

      Results

      Patient and tumor characteristics

      We identified 357 cases of ILC treated with mastectomy. Of these, 182 (51%) underwent a simple mastectomy, 120 (33.6%) underwent a total skin-sparing mastectomy, and 55 (15.4%) underwent a skin-sparing mastectomy. Average age at diagnosis was 57, ranging from 28 to 89 years. The majority of cases were estrogen receptor (ER) positive and human epidermal growth factor receptor-2 (HER2) negative (92.3%). Most patients had stage I-II disease (79.6%), with 45.8% having node positive disease (Table 1). Of the 357 cases, 261 (73.1%) had a mastectomy as their initial operation, 77 (21.6%) underwent mastectomy after one prior attempt at breast conservation, and 19 (5.3%) underwent mastectomy after two prior attempts at breast conservation.
      Table 1Patient and tumor characteristics.
      CharacteristicN (%)
      Age, years (mean, SD)56.8, 11.7
      Tumor grade
      Data available in n = 338.
       196 (28.4%)
       2222 (65.7%)
       320 (5.9%)
      Receptor subtype
      Data available in n = 303.
       ER+/PR+/Her2-237 (76.5%)
       ER+/PR-/Her2-49 (15.8%)
       Her2+15 (4.8%)
       Triple Negative9 (2.9%)
      Lymphovascular invasion34 (9.5%)
      Pleomorphic histology42 (11.8%)
      Nodal Stage
       N0192 (53.8%)
       N1102 (28.6%)
       N235 (9.8%)
       N328 (7.8%)
      T Stage
       T1124 (34.7%)
       T2110 (30.8%)
       T3123 (34.4%)
      Tumor Size (cm, SD)4.1, 3.4
      ER estrogen receptor, PR Progesterone receptor, Her2 human epidermal growth factor receptor 2.
      a Data available in n = 338.
      b Data available in n = 303.

      Positive margin rates

      The overall positive margin rate after mastectomy was 10.6%, with 38 cases having at least one positive margin. Among the 261 patients who had mastectomy as the first operation, the positive margin rate was 11.5% (30/261). Of those, positive margin location was anterior in 8 (26.7%), deep in 4 (13.3%), at nipple base in 3 (10%), radial in 2 (6.7%), involving multiple margins in 2 (6.7%), and missing in 10 (33%). Among the 77 patients who had mastectomy as their second operation, the positive margin rate was 7.8% (6/77). Of those, positive margin location was anterior in 3 (50%), deep in 1 (16.7%), and missing in 2 (33.3%). Among the 19 patients who had mastectomy as their third operation, the positive margin rate was 10.5% (2/19), with location being anterior in one, and missing in the other.

      Factors associated with positive margins after mastectomy

      There was no difference in age, tumor grade, receptor subtype, presence of pleomorphic histology, presence of lymphovascular invasion, or N stage in cases with a positive margin versus those with negative margins. Increasing T stage was significantly associated with having a positive margin, with a positive margin rate of 1.6% in T1, 11.8% in T2, and 18.7% in T3 tumors (p < 0.001). The mean tumor size among those with positive margins was 6.5 cm versus 3.8 cm among those with negative margins (p < 0.0001, Table 2).
      Table 2Factors associated with positive margins after mastectomy.
      Positive Margins (n = 38)Negative Margins (n = 319)P value
      Age in years (mean, SD)57.8, 13.356.7, 11.50.563
      Tumor grade (n = 338)0.998
       110 (28.6%)86 (28.4%)
       223 (65.7%)199 (65.7%)
       32 (5.7%)18 (5.6%)
      Receptor subtype0.655
       ER+/PR+/Her2-27 (77.1%)210 (76.4%)
       ER+/PR-/Her2-4 (11.4%)45 (16.4%)
       Her2+2 (5.7%)13 (4.7%)
       Triple negative2 (5.7%)7 (2.5%)
      Lymphovascular invasion4 (10.5%)30 (9.4%)0.609
      Pleomorphic histology7 (18.4%)35 (10.9%)0.178
      Nodal Stage0.244
       016 (42.1%)176 (55.2%)
       111 (28.9%)91 (28.5%)
       26 (15.8%)29 (9.1%)
       35 (13.2%)23 (7.2%)
      T stage<0.001
       12 (5.2%)122 (38.2%)
       213 (34.2%)97 (30.4%)
       323 (60.5%)100 (31.3%)
      Tumor size (cm, SD)6.5, 3.73.8, 3.3<0.0001

      Management strategies for positive margins

      Of the 38 cases with positive mastectomy margins, 9 (23.7%) had no additional local therapy, while 8 (27.6%) underwent re-excision, 21 (55.3%) received post-mastectomy radiation (PMRT), and 5 (17.2%) underwent both re-excision and radiation (Fig. 1). Among the 13 patients who had a re-excision for positive margins after mastectomy, 11 had clear final margins while 2 had persistently positive margins; both patients with persistently positive margins also received PMRT. When comparing those with positive mastectomy margins who received additional local therapy versus those who did not, there was no difference in tumor size, presence of pleomorphic histology, presence of lymphovascular invasion, T category, N category, overall stage, or receptor subtype. The only factor associated with receiving additional local therapy for a positive margin was younger age (mean age was 55.0 years in those undergoing additional local therapy versus 66.8 years in those who did not, p = 0.0184, Table 3).
      Fig. 1
      Fig. 1Flow chart of outcomes of patient who underwent mastectomy for management of ILC.
      Table 3Factors associated with treatment of positive margins following mastectomy.
      Additional local therapy (n = 29)No additional local therapy (n = 9)P value
      Age in years (mean, SD)55.0, 11.366.8, 15.80.0184
      Tumor grade0.336
       19 (34.6%)1 (11.1%)
       216 (61.5%)7 (77.8%)
       31 (3.9%)1 (11.1%)
      Receptor subtype0.228
       ER+/PR+/Her2-23 (82.1%)4 (57.1%)
       ER+/PR-/Her2-2 (7.1%)2 (28.6%)
       Her2+2 (7.1%)0 (0%)
       Triple negative1 (3.6%)1 (14.3%)
      Tumor size (cm, SD)5.28, 3.76.9, 3.60.245
      Pleomorphic Histology5 (17.2%)2 (22.2%)0.736
      Lymphovascular Invasion2 (5.9%)2 (22.2%)0.366
      T Stage0.442
       11 (3.5%)1 (11.1%)
       29 (31%)4 (44.4%)
       319 (65.5%)4 (44.4%)
      N Stage0.695
       013 (44.8%)3 (33.3%)
       19 (31%)2 (22.2%)
       24 (13.8%)2 (22.2%)
       33 (22.2%)2 (22.2%)
      In the entire cohort, PMRT was used in 76 (24.6%) cases in the negative margin group, and 21 (55.3%) cases in the positive margin group (p < 0.001). On multivariate logistic regression, having positive margins was associated with significantly higher odds of undergoing PMRT (odds ratio 4.4, 95% confidence interval [CI] 1.6–11.9, p = 0.004). Other factors significantly associated with receiving PMRT were younger age, higher T stage, higher N stage, receptor subtype, and grade 3 tumors. There was no difference in the use of adjuvant chemotherapy, as 31.5% of those with a positive margin received adjuvant chemotherapy versus 33.7% of those who had negative margins.

      Association between positive margins and outcomes

      On univariate analysis, having a positive mastectomy margin was associated with significantly shorter RFS compared to those with negative margins (p = 0.0015). In a multivariable Cox proportional hazards model adjusting for age, stage, tumor grade, receptor subtype, and receipt of adjuvant endocrine therapy, having positive margins remained significantly associated with shorter RFS (hazard ratio [HR] 2.64, 95% confidence interval [CI] 1.14–6.1, p = 0.023) (Table 4).
      Table 4Cox proportional hazards model for factors associated with recurrence free survival.
      Hazard Ratio95% Confidence IntervalP value
      Age in years1.000.96–1.040.955
      Overall Stage
      1Reference
      21.180.53–2.610.683
      32.411.01–5.740.048
      Grade
      1Reference
      20.730.35–1.510.397
      33.841.11–13.230.033
      Receptor Subtype
      ER+/PR+/Her2-Reference
      ER+/PR-/Her2-1.950.77–4.920.158
      Her2+4.111.08–10.210.039
      Triple negative3.211.01–10.220.049
      Endocrine Therapy0.430.19–0.990.048
      Positive Margin2.641.14–6.100.023
      Among those with positive margins, those who had additional local therapy (either re-excision, radiation, or both) had significantly improved RFS (p = 0.0086, Fig. 2). In a multivariable Cox proportional hazards model adjusting for age and tumor size, undergoing treatment for positive margins was associated with significantly improved RFS (HR 0.097, 95% CI 0.02–0.47, p = 0.004) while each additional centimeter of increased tumor size was associated with a 25% increased risk of local or distant recurrence (HR 1.25, 95% CI 1.02–1.52, p = 0.028).
      Fig. 2
      Fig. 2Kaplan Meier curve of recurrence free survival for patients who underwent treatment for positive margins versus those who didn't.
      In the overall cohort, being aged 50 years or older was associated with significantly improved RFS compared to being aged under 50 on unadjusted analyses (p = 0.03, log rank test). However, among those with positive mastectomy margins, there was no difference in RFS by age on univariate analysis. Similarly, on multivariate analysis adjusting for undergoing additional local therapy for positive mastectomy margins, age was not associated with RFS.

      Discussion

      There are several findings from this study that may impact management strategies of patients with ILC. Mastectomy resulted in a high positive margin rate, particularly for those with T3 tumors. Indeed, larger tumor size was the primary predictor of positive margin status after mastectomy. We also found that additional local therapy can mitigate the increased risk of recurrence associated with positive margin status. In this dataset, patients of older age were significantly less likely to undergo such additional local therapy in the setting of positive margin—a finding that should be investigated further in other datasets.
      Comparing the rate of positive mastectomy margins found in this series of patients with ILC to those reported in the literature is challenging due to heterogeneity between studies. Many studies include “close” margins, with varying definitions of margin width, in their analyses of patients with positive mastectomy margins. Indeed, studies that include such close margins typically describe higher rates of positive margins (up to 27%) than those that use the definition of no ink on tumor (rates range from 3 to 9%).
      • Sledge G.
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      Collective wisdom: lobular carcinoma of the breast.
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      Positive nipple margins in nipple-sparing mastectomies: rates, management, and oncologic safety.
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      • Sheikh F.
      • Rebecca A.
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      • et al.
      Inadequate margins of excision when undergoing mastectomy for breast cancer: which patients are at risk?.
      Importantly, the optimal margin width after mastectomy has not been well defined, with a recent systematic review suggesting that perhaps wider margins than no ink on tumor would be beneficial to reduce locoregional recurrence after mastectomy.
      • Wasif N.
      • Maggard M.A.
      • Ko C.Y.
      • Giuliano A.E.
      Invasive lobular vs. Ductal breast cancer: a stage-matched comparison of outcomes.
      To our knowledge, this report is the first to focus specifically on margins after mastectomy in ILC. Two large studies examining locoregional recurrence after mastectomy report histology and include ILC patients, but do not provide specific rates of positive margins by histology or stage. Hastings et al. evaluated 1259 patients with T1 invasive breast cancers, including 225 patients with lobular histology.
      • Hastings J.
      • Iganej S.
      • Huang C.
      • Huang R.
      • Slezak J.
      Risk factors for locoregional recurrence after mastectomy in stage T1 N0 breast cancer.
      They found an overall positive margin rate of 8.5%, with no difference in rates of recurrence between patients with ILC versus IDC. Maishman et al. evaluated 1464 patients who underwent mastectomy for invasive cancer, including 135 with lobular histology.
      • Maishman T.
      • Cutress R.I.
      • Hernandez A.
      • et al.
      Local recurrence and breast oncological surgery in young women with breast cancer.
      The overall positive margin rate in this series was 8.9%, using margin width of 0 mm to define positive margins. In our series, we found a positive mastectomy margin rate of 10.6%, which is consistent with the reported ranges in these studies that include mostly patients with ductal histology. Importantly, however, we found a positive margin rate of 18.7% in T3 ILC cases undergoing mastectomy. Our definition of positive margin was no ink on tumor; had we included close margins as many other reports do, this rate would undoubtedly be higher. We can conclude that patients with large ILC tumors are particularly at risk for positive margin even after mastectomy; this is especially relevant since diffusely growing lobular tumors are often diagnosed at later stages than IDC.
      • Wasif N.
      • Maggard M.A.
      • Ko C.Y.
      • Giuliano A.E.
      Invasive lobular vs. Ductal breast cancer: a stage-matched comparison of outcomes.
      Our finding of an association between positive mastectomy margins and significantly worse RFS is also consistent with other studies in the literature. Several retrospective series and a large systematic review demonstrate higher risk of locoregional failure for those with positive margins after mastectomy for both invasive and in situ disease.
      • Hastings J.
      • Iganej S.
      • Huang C.
      • Huang R.
      • Slezak J.
      Risk factors for locoregional recurrence after mastectomy in stage T1 N0 breast cancer.
      • Maishman T.
      • Cutress R.I.
      • Hernandez A.
      • et al.
      Local recurrence and breast oncological surgery in young women with breast cancer.
      • Bundred J.
      • Michael S.
      • Bowers S.
      • et al.
      Do surgical margins matter after mastectomy? A systematic review.
      • Rashtian A.
      • Iganej S.
      • Amy Liu I.-L.
      • Natarajan S.
      Close or positive margins after mastectomy for DCIS: pattern of relapse and potential indications for radiotherapy.
      While risk is increased, the magnitude of risk appears to differ based on patients characteristics like age. Childs et al. found that the absolute risk of locoregional recurrence for those with positive margins was low, remaining under 5% at a median of 6.7 years of follow up.
      • Childs S.K.
      • Chen Y.-H.
      • Duggan M.M.
      • et al.
      Surgical margins and the risk of local-regional recurrence after mastectomy without radiation therapy.
      However, other investigators show locoregional failure rates approaching 25% in patients under the age of 50 with positive margins.
      • Freedman G.M.
      • Fowble B.L.
      • Hanlon A.L.
      • et al.
      A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger.
      Such discrepancies influence guidelines for recommending PMRT, where younger age is a consideration because of its association with increased recurrence risk. This may also impact providers’ decision-making, as reflected in the significantly lower rates of either re-excision or PMRT in older patients in our cohort.
      When positive margins occur after mastectomy, determining the optimal treatment strategy can be challenging. While re-excision after breast conserving surgery is well described, re-excision rates after mastectomy are not well studied. In some cases, surgeons may feel that the extent of prior resection (e.g. from dermis to muscle) might preclude additional resection at the site of a pathologically positive margin. Additionally, locating the correct area to re-excise after mastectomy can be challenging, and typically requires multidisciplinary review of imaging and mapping of the mastectomy specimen with the evaluating pathologist. While the presence of a positive margin is not clearly an indication for PMRT, especially in patients with early stage disease, our findings support its consideration in those with ILC histology and positive margin after mastectomy.
      • Buchholz T.A.
      • Somerfield M.R.
      • Griggs J.J.
      • 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.
      ,
      • Sheikh F.
      • Rebecca A.
      • Pockaj B.
      • et al.
      Inadequate margins of excision when undergoing mastectomy for breast cancer: which patients are at risk?.
      ,
      • Truong P.T.
      • Olivotto I.A.
      • Speers C.H.
      • Wai E.S.
      • Berthelet E.
      • Kader H.A.
      A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer.
      The 2016 American Society for Radiation Oncology (ASTRO) guidelines support PMRT for those with T1-2 tumors and 1–3 positive nodes due to improvements in locoregional failure, recurrence and breast cancer mortality.
      • Recht A.
      • Comen E.A.
      • Fine R.E.
      • et al.
      Postmastectomy radiotherapy: an American society of clinical Oncology, American society for radiation Oncology, and society of surgical Oncology focused guideline update.
      However, controversy remains for those with T1-2 tumors and one involved node. In those situations, other risk factors such as age, grade, LVI and hormone receptor status are often considered. Positive margins may not be a factor mentioned in ASTRO guidelines, but there are some data to support its use to lower recurrence risk in the setting of positive mastectomy margins.
      • Nielsen H.
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      • Grau C.
      • Jensen A.
      • Overgaard J.
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      ,
      • Kaššák F.
      • Rossier C.
      • Picardi C.
      • Bernier J.
      Postmastectomy radiotherapy in T1-2 patients with one to three positive lymph nodes – past, present and future.
      However, the benefit of PMRT for preventing locoregional recurrence in those with positive or close mastectomy margins appears greatest in those under the age of 50 in studies of largely ductal breast cancer.
      • Freedman G.M.
      • Fowble B.L.
      • Hanlon A.L.
      • et al.
      A close or positive margin after mastectomy is not an indication for chest wall irradiation except in women aged fifty or younger.
      ,
      • Truong P.T.
      • Olivotto I.A.
      • Speers C.H.
      • Wai E.S.
      • Berthelet E.
      • Kader H.A.
      A positive margin is not always an indication for radiotherapy after mastectomy in early breast cancer.
      In our cohort, we found that in general older patients with ILC had significantly improved RFS compared to younger patients. In those with positive margins however, the absence of additional locoregional therapy led to a loss of the RFS advantage seen in older patients. While subgroups were too small to evaluate the benefit of PMRT specifically by age in our cohort, it appears that the absence of additional locoregional treatment in older patients was indeed associated with worse outcomes.
      This association between older age and less local therapy in our study was an unexpected finding. This is consistent with the broad idea of de-escalating interventions in those with competing mortality risks, who will likely benefit less. The “Choosing Wisely” campaign was launched by the American Board of Internal Medicine in 2012 to work to reduce low-value care.
      • Neuner J.M.
      • Nattinger A.B.
      • Yen T.
      • McGinley E.
      • Nattinger M.
      • Pezzin L.E.
      Temporal trends and regional variation in the utilization of low-value breast cancer care: has the Choosing Wisely campaign made a difference?.
      As part of this, in 2016 the Society of Surgical Oncology recommended surgeons not routinely use sentinel lymph node biopsy in clinically node negative women older than 70 with hormone receptor positive breast cancer.
      • Martelli G.
      • Miceli R.
      • Daidone M.G.
      • et al.
      Axillary dissection versus no axillary dissection in elderly patients with breast cancer and no palpable axillary nodes: results after 15 years of follow-up.
      ,
      • Hughes K.S.
      • Schnaper L.A.
      • Bellon J.R.
      • et al.
      Lumpectomy plus tamoxifen with or without irradiation in women age 70 Years or older with early breast cancer: long-term follow-up of CALGB 9343.
      Results from CALGB 9343 and PRIME II suggest that adjuvant radiation following breast conserving surgery in elderly patients does not improve overall survival.
      • Hughes K.S.
      • Schnaper L.A.
      • Bellon J.R.
      • et al.
      Lumpectomy plus tamoxifen with or without irradiation in women age 70 Years or older with early breast cancer: long-term follow-up of CALGB 9343.
      ,
      • Kunkler I.H.
      • Williams L.J.
      • Jack W.J.L.
      • Cameron D.A.
      • Dixon J.M.
      Breast-conserving surgery with or without irradiation in women aged 65 years or older with early breast cancer (PRIME II): a randomised controlled trial.
      It is possible that the overall trend towards fewer interventions in older women, particularly when survival is not impacted, is reflected in the management strategies seen in our cohort. However, our finding that omission of local therapy for positive margins was significantly associated with reduced RFS suggests that interventions may be beneficial, even in older patients. The association between positive margins and worse outcomes persisted even when adjusting for adjuvant endocrine therapy use suggesting that further local therapy is necessary to prevent recurrence in these ER positive breast cancers. The association between older age and reduced local therapy for positive margins warrants further investigation in other series to determine if this reflects a nationwide trend, given current efforts to de-escalate care in some older patients.
      While our study provides unique insight into positive margin rates after mastectomy in ILC and the potential impact of additional local therapy, its retrospective nature lends itself to limitations. We do not know whether therapy decisions were driven by patient preference or provider recommendation. Additionally, we had too few cases to specifically compare re-excision versus PMRT as the optimal management strategy. However, this is the largest series examining positive margin rates in ILC after mastectomy, which is a challenging clinical problem to treat.

      Conclusions

      In summary, these data will help guide local therapy decisions and management strategies for women with ILC. The association between large tumor size and positive margins is particularly salient, given the tendency of ILC to present at advanced stages. This highlights the importance of developing optimal systemic treatment options to reduce tumor volume prior to surgical excision, even in the setting of mastectomy. These findings should help set expectations for surgical therapy and suggest that either re-excision or PMRT should be considered for those patients with ILC and positive margins after mastectomy.

      Disclosures

      None.

      Declaration of competing interest

      The authors have no conflicts of interest.

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