There is controversy in the management of the lobular intraepithelial neoplasia (LIN), namely atypical lobular hyperplasia (ALH)/lobular carcinoma in situ (LCIS) diagnosed by core needle biopsy without other proliferative lesions such as atypical ductal hyperplasia (ADH), ductal carcinoma in situ (DCIS), or invasive carcinomas. Some recommend excisional biopsy and others support no excision. There is consensus amongst pathologists, however, regarding the margin assessment of LIN on excisional biopsy; it is not mandatory to report LIN at the margin as in DCIS or invasive carcinoma and most pathologists do not report LIN at the margin. Obtaining a margin clear of LIN is not a surgical goal. Generally, the presence of LIN at the lumpectomy margin is regarded as irrelevant by most clinicians. The lack of consensus on this topic is illustrated by the results of a recent online survey by the American Society of Breast Disease. The survey posed the question of appropriate management of a patient with LCIS at the margin of a lumpectomy for invasive cancer. 40% of those who replied stated that they would consider re-excision in this circumstance and 8% stated that they would always perform a re-excision. (Observation from American Society of Breast Disease. ASBD Advisor 2008; Feb 17).
Also, unlike DCIS, patients with LIN alone on excision are not treated with radiation after breast conservation therapy unless there is a concomitant DCIS or invasive carcinoma. With emerging new evidence that LIN is not just a risk factor but a precursor lesion to invasive carcinoma, margin status may play an important role in the treatment of patients with LIN. If LIN is indeed a precursor lesion, then its presence at the surgical margin in a lumpectomy specimen should increase local recurrence in patients treated with breast-conserving therapy. In an attempt to test this hypothesis, we compared local residual/recurrence rates in patients with and without LIN at the margin who underwent breast conservation surgery for the treatment of invasive carcinoma or DCIS. Ideally, the positive and negative control groups should have a similar disease process except for margin status. The positive group included some cases that had no cancer/DCIS, i.e. only LCIS, with LCIS/ALH at the margin but the negative group did not have any cases that had only LCIS/ALH in the specimen. This was done so that our study would underestimate rather than possibly overestimate the risk of having LIN at the margin, especially given the fact that it is clinically a short-term follow-up.
As it is often difficult to differentiate between a local recurrence and a new primary in the treated breast, all tumor found in the ipsilateral breast during follow-up were classified as local recurrences in our study. Technically it shouldn't be considered as recurrences, but considered as residual tumor because the cancer was probably there at the time of initial resection, and not progressed from the margin LIN.
Our study showed 39% had significant recurrent diseases when LIN was seen at the surgical margin of initial breast conservation therapy, compared to 7.9% from negative control group. This 7.9% includes patients with metastasis in the negative group, but the 39% from positive group counts only local recurrence.
There are limited numbers of LIN recurrence data after only breast conservation therapy. The reported frequencies of recurrence of invasive carcinoma after LCIS diagnosis is approximately 10% and 20% of patients at 10 years and 20 years, respectively. The survival rate at 15 years was 100% in a cohort of 32 patients [6–8].
The NSABP B-17 study analyzed a subset of 182 patients with LCIS in addition to DCIS and treated with breast conservation therapy alone was compared to DCIS alone in the incidence of recurrence. The ipsilateral recurrence of LCIS and DCIS was significantly lower than DCIS alone; 2.2% in LCIS and DCIS and 12% in the DCIS alone respectively. Also, the contralateral breast recurrence incidence was 1.1% compared to 9% respectively. Their conclusion was that the presence of LCIS should not lead to more surgery such as mastectomy .
A similar conclusion was drawn from Carolin K et al.  study which compared LCIS and invasive cancer group to invasive cancer without LCIS; there was no significant increase in ipsilateral or contralateral breast recurrence in a total of 105 patients with LCIS and 115 patients without LCIS. Over time, there was no increase in relapse noted for the patients who had LCIS as a histologic component of invasive carcinoma.
Jobsen et al.  looked at the impact of margin status and outcome of invasive lobular carcinoma treated with breast-conserving therapy and followed the long term outcome from a single region in the Netherlands during the last twenty years with 318 patients and 33 re-excision. They found that the positive margins for ILC seem to be a strong predictor for local recurrence in women less than or equal to 50 years of age but the distant metastasis free survival and disease free survival were not affected by the margin status. LCIS alone did not show significance in relation to local control. Their study showed a trend towards an increased local recurrence rate with positive margins for LCIS only and this seems limited to women greater than 50-years of age.
Robin M. Ciocca et al.  studied whether or not LCIS at the margin would increase local recurrence in patients treated with breast-conserving therapy. In their 84 patients with LCIS present at the specimen margin, the crude rate of local recurrence for patients with and without LCIS was 4.5% and 3.8% respectively. They concluded that re-excision is not indicated even if LCIS is present at the margin.
Jolly et al.,  on the contrary, found that the presence of LCIS was associated with a higher incidence ipsilateral recurrence; 14% with LCIS at the margin when compared to 7% without LCIS at the margin from a patient sample of 56 with a median of 8.7 years follow up.
Stolier A et al.  reported no local recurrence with LCIS in 40 patients with 38% involved or close margin with LCIS in 67 months follow-up period. Ben-David M et al.  reported that the presence of LCIS at the margins and the multifocal extent of LCIS did not alter the rate of local recurrence in their 64 patients' samples who received breast conservation and radiation treatment with the median follow-up time of 3.9 years. Abner et al.  reported similar results; that the extent of LCIS and positive margin with LCIS did not have increased local recurrence rate in 8 years. Sasson et al.  reported that the ipsilateral local recurrence rate of 29% in the LCIS group as opposed to 6% in the generally treated population. However, when tamoxifen treatment was used as hormonal therapy, the difference was not significant; 8% as opposed to 6%, comparing the LCIS group to the control group.
Literature supports that with the incidences of ipsilateral and contralateral recurrence rates, mortality rates are low with LIN, and even with invasive lobular carcinoma. This may be due to the fact that the development of invasive carcinoma after LIN takes a long time. Most of the studies have a short median follow-up and cannot exclude the possibility that, with a longer follow-up duration, an impact of LIN on local recurrence will be significantly increased. In fact, the study of Rosen et al. reported the average interval to the development of cancer was 20.4 years after biopsy . Another study by Page et al.  showed 75% of cancers developed within 15 years of biopsy of LCIS.
Long term follow-up of LIN treated with BCT alone has demonstrated a 1% per year cumulative long-term risk of breast carcinoma persisting even 10-20 years after diagnosis. Like most retrospective studies, the inability to prospectively evaluate the conclusions and hypotheses is a limiting factor, as well as a short term follow up in LIN. Clinical follow-up of more than 5 years is needed to verify the significance of LIN in the ipsilateral recurrence. Prospective randomized trials related to therapy of patients with LIN at the margin are needed to clearly understand the risk of local recurrence. However, a low mortality rate supports the view that mastectomy is not indicated to clear LIN at the margin if LIN is classic type and grade 1. If there is an overlapping feature of LCIS with DCIS, then re-excision is not unreasonable.
There is no doubt that LIN is a risk factor for subsequent carcinoma, and morphologic, immunohistochemical and epidemiologic observations support the statement that LIN is also a direct precursor to invasive carcinoma. Although our data is limited due to the fact that it is a retrospective study and small in sample size, such data would only add to the limited number of LIN recurrence rate after breast conservation therapy. The limitation of our study is that there may be follow-up bias. In our negative control group, there are not any additional surgeries so we cannot be sure that there are no cancerous lesions in the control group.