- Open Access
Lobular carcinoma in situ (LCIS) of the breast: is long-term outcome similar to ductal carcinoma in situ (DCIS)? Analysis of 200 cases
© Cutuli et al.; licensee BioMed Central. 2015
Received: 4 January 2015
Accepted: 16 March 2015
Published: 6 May 2015
Lobular carcinomas in situ (LCIS) represent 1-2% of all breast cancers. Both significance and treatment remain widely debated, as well as the possible similarities with DCIS.
Materials and methods
Two hundred patients with pure LCIS were retrospectively analyzed in seven centres from 1990 to 2008. Median age was 52 years; 176 patients underwent breast-conserving surgery (BCS) and 24 mastectomy. Seventeen patients received whole breast irradiation (WBRT) after BCS and 20 hormonal treatment (15 by tamoxifen).
With a 144-month median follow-up (FU), there were no local recurrences (LR) among 24 patients treated by mastectomy. With the same FU, 3 late LR out of 17 (17%) occurred in patients treated by BCS and WBRT (with no LR at 10 years). Among 159 patients treated by BCS alone, 20 developed LR (13%), but with only a 72-month FU (17.5% at 10 years). No specific LR risk factors were identified. Three patients developed metastases, two after invasive LR; 22 patients (11%) developed contralateral BC (59% invasive) and another five had second cancer.
LCIS is not always an indolent disease. The long-term outcome is quite similar to most ductal carcinomas in situ (DCIS). The main problems are the accuracy of pathological definition and a clear identification of more aggressive subtypes, in order to avoid further invasive LR. BCS + WBRT should be discussed in some selected cases, and the long-term results seem comparable to DCIS.
Firstly described in 1941 by Muir, Foote and Stewart, the exact significance of lobular carcinoma in situ (LCIS), also called lobular neoplasia (LN), remains debated, ranging for many years from a simple marker of subsequent invasive carcinoma to, more recently, a real pre-cancerous lesion in many cases, especially invasive lobular carcinoma (ILC) [1,2].
The variability of pathological definitions according to time, with frequent combined analysis of LCIS/LN and atypical lobular hyperplasia (ALH) or new classification defined in 2002 and including three types of lobular intra-neoplasia (LIN), as well as rarity and frequent insufficient long-term follow-up in several series, all represent additional uncertainties regarding its optimal treatment .
Our study evaluated the long-term outcome in a cohort of 200 women with pure LCIS treated by three different options, i.e. breast-conserving surgery alone (BCS), BCS with whole breast irradiation (BCS + WBRT) or mastectomy (M). We compared our results according to the same treatments used in DCIS [4,5], particularly assessing the potentially life-threatening risk of invasive local recurrence (LR).
Materials and methods
From January 1990 to December 2008, 200 patients with “pure” LCIS (without associated DCIS and/or previous or synchronous contralateral DCIS or invasive breast cancer) were retrospectively collected in seven centres, also sometimes including benign lesions, e.g. atypical (ductal and/or lobular) hyperplasia or sclerosing adenosis. Seven patients had bilateral synchronous LCIS. Median age was 52 years (range: 32–77).
79 out of 180 (44%) patients were post-menopausal and 45 of them (57%) underwent hormonal replacement therapy (HRT) for a 5-year median duration (76% by estrogen and progestins association).
In 60 out of 166 (30%) specified cases, a first and/or second family-history degree of breast cancer was found. Two patients had BRCA-1 and 2 mutation.
Radiological features leading to biopsy (183 evaluable cases)
Microcalcifications and other abnormalities
168 patients underwent lumpectomy (7 with a complementary resection), 8 quadrantectomy and 24 (6 in two times) mastectomy (nine of whom had contralateral prophylactic mastectomy), due to multicentric disease or patient's preference.
Seventeen patients underwent a classical 50 Gy/25 fractions WBRT, including 8 with a 10-Gy boost. There were no factors influencing the WBRT choice, i.e. age, LIN subtype, excision quality or multifocality.
Hormonal therapy (HT)
Twenty patients received hormonal therapy (15 by Tamoxifen), 17 of them after BCS (10.7%), two after BCS + RT (11.8%) and only one after mastectomy. HT was significantly more prescribed in case of incomplete excision (16% versus 4.5%, p = 0.041) or LIN 3 or 2 versus 1 (43%, 15% and 4% respectively, p = 0.03).
All centres had pathologists deeply involved in the breast field, but central review could not be carried out. The subtype was only specified in 128 cases (classical in 124 and pleomorphic in 4).
According to LIN classification (applied since 2002), among our 94 evaluable cases, we found 25 LIN 1, 54 LIN 2 and 15 LIN 3. Moreover, among 172 evaluable cases, a single focus of LCIS was found in 101 patients (59%) and multiple foci in 71 (41%). The multiple foci rate was significantly higher (p = 0.001) in patients treated by mastectomy (77.3%) versus BCS (+/−WBRT) (36%). Among 143 evaluable cases, excision was considered complete in 112 (78%) cases, incomplete in 13 (9%) and doubtful in 18 (13%). Among 75 evaluable cases, the median lesion size was 12 mm.
Moreover, associated atypical epithelial hyperplasia (AEH), atypical lobular hyperplasia (ALH) and sclerosing adenosis were found in 68/187 (36%), 48/184 (26%) and 46/181 (25%) of the cases respectively.
An associated axillary nodal involvement (ANI) was found in three cases (two ILC and one IDC). One patient treated by mastectomy developed axillary recurrence 20 years later certainly due to missed foci of invasive carcinoma in the mastectomy specimen. Thus, the overall axillary recurrence rate for the entire cohort was 2% (4/200).
Three patients developed metastases, two with previous invasive LR (one ILC and one IDC). Thus, the rate of metastasis after invasive LR was 11% (2/18).
Contralateral breast cancer (CBC)
Contralateral breast cancer (CBC) according to treatment
In situ (n)
BCS + WBRT*** (17)
Five patients developed a second cancer (colon: 2, thyroid: 1, skin and salivary gland: one each).
Six patients were lost of follow-up and 189 are still alive. Four patients died, one by BC, one by intercurrent disease and two by colic cancer.
Incidence and epidemiology
Due in large part to increased mammographic screening, DCIS incidence increased 7.2 fold in the USA from 1980 to 2001 and LCIS 2.6 fold [6,7]. Similar trends were observed in other Western countries . The median age at diagnosis in most LCIS series varies from 45 to 50 years [1,8], i.e. 7–8 years younger than in the DCIS series . Few data suggest a possible LCIS increase due to hormone replacement therapy (HRT) . In our series, 57% of 79 menopausal women received HRT. Despite the possible discovery by clinical symptoms, very often due to benign associated lesions (cyst or fibroadenoma), our series confirms that about 65% of LCIS were discovered by clustered microcalcifications, such as reported by other studies [9,10]. From a pathological point of view, the distinction between LCIS and ALH is sometimes difficult and subjctive. Both lesions are often associated [11-13] and finally represent a temporal continuum in which the extent of lobular involvement varies . Moreover, the loss of E-cadherin expression characterizes LCIS, facilitating a distinction from ductal lesions.
Significance of LCIS and possible underestimation at core-needle biopsy (CNB)
For many years, LCIS (only representing 1-2% of all breast cancers) has just been considered a marker of risk for subsequent (in situ or invasive) cancer in both breasts . The discovery by mammography or presence of another benign lesion leads to a complementary excision after CNB only in a variable part of cases, ranging from 40% to 70% in the literature and without clear selection criteria. Some authors proposed surveillance or complementary excision according to several and often different parametres, sometimes including «lobular neoplasia» encompassing both LCIS and ALH. In a large review by Hussain , including 31 studies, 789 out of 1229 (64%) patients diagnosed with LN on CNB had surgical excision: 280 were classified ALH, 241 LCIS, 22 pleomorphic LCIS (PLCIS) and 246 unspecified LN. In this review, the overall underdiagnosis rate.
(DCIS and/or invasive BC at subsequent excision) was 27% (211 out of 789). In a wide series from New York, among 201 out of 285 (71%) excisions performed for LN after CNB, 26 (13%) were upgraded; 7 had DCIS, 9 ILC and 10 IDC . However, the risk of underestimated malignancy at subsequent excision (DCIS or infiltrating carcinoma) was only 8% (DCIS: 2.7% and infiltrating BC: 5.3%) among 478 lesions in a literature review reported by Murray, but with wide variations (from 3% to 35%) . Finally, the initial underestimation risk after CNB showing LCIS or ALH is quite difficult to assess, without clear predictive criteria in the literature .
Potential risk of LCIS invasiveness
Such as for DCIS, the potential LCIS risk is invasive BC development, keeping in mind that both lesions are theoretically initially fully curable. Compared to women in the general population, those with LCIS have a minimum 5–6 fold higher risk of IBC . This risk increases in case of associated lesions (AH)  and especially when first-degree family history of BC was present , almost reaching the risk (8–10 fold) of women with BRCA 1–2 mutations. These data confirm the crucial importance of identifying the most «aggressive» LCIS subtypes leading to invasive BC.
Comparisons between DCIS and LCIS treatments
DCIS now represent 15 to 20% of all breast cancers (63 000 cases in the USA in 2014) and are considered long-term precursors of invasive BC in 40-50% of the cases, even in low-grade lesions . However, DCIS encompass several heterogeneous lesions due to many biological and molecular features leading to variable progressions to invasion. There are much more DCIS treatment data than for LCIS [13,17,18].
Mastectomy remains performed in 30-42% of DCIS according to the series [19,20], due to extension of the lesions, multicentricity and/or patients' preference. The local control rate was about 98% . On the other hand, very few data are available on mastectomy rate in LCIS [7,13]. In our series, multicentricity seemed to be a factor leading to mastectomy.
In a recent American report using the Surveillance, Epidemiology and End Results (SEER) database, among 11 641 patients diagnosed with LCIS from 2000 to 2009, 16% underwent mastectomy, but with large differences based on geographic areas and age (from 12% to 24%) . The local control rate, such as in our 24 patients, was almost 100%.
Due to more frequent discovevry of «small lesions», a conservative approach was gradually used in DCIS [17,18]. The standard treatment includes BCS and whole breast irradiation (WBRT) according to four large randomized trials (combined in a meta-analysis including over 4 500 cases) and retrospective studies showing that WBRT halfed the local recurrence rates (LR), both in situ and invasive [21-25]. Consequently, for these lesions, the 10-year LR rates are about 5-8% in the most recent series [26-28], reaching only 1% at 7 years in the very selected study on low-risk DCIS by RTOG . However, in 20-25% of the cases, for various reasons, WBRT is not used in DCIS, leading, even in very selected cases (small lesions, wide margins, low grade), to a 15-20% 10-year LR rate, half of which invasive [30,31].
This is a crucial problem, because now several studies confirm the unfavourable impact of invasive LR in patients treated for DCIS with a 12-18% long-term of metastatic evolution [21,22,32]. For LCIS, there are no clear therapeutic guidelines, both after CNB and surgical excision [1,2,9]. The previously SEER-quoted study  showed that 10% of the patients had biopsy alone (precise criteria for the choice not specified) and 73% excision alone, whereas only 1% (116 patients) underwent complementary WBRT, without specific choice criteria or data on local control.
In comparison with DCIS, the slope of the LR curve for LCIS seems quite less sharp and more spread out in time (see Figure 1), suggesting that the overall cancerization process was slower.The increase of local recurrence rates due to young age and incomplete excision (close and/or positive margins) is not clearly documented in LCIS compared to DCIS. However, few LCIS subtypes, e.g. pleomorphic LCIS, very extensive LCIS (with over ten involved acini) or LCIS with a great amount of necroses, seem to be clearly more aggressive lesions [3,9] and should be treated such as DCIS, as suggested by 2009 French Breast Carcinoma in Situ guidelines (www.e-cancer.fr).
Therefore, in these aggressive LCIS, WBRT addition should be discussed in the multidisciplinary team, in order to minimize the LR risk. In our previous report, we observed only one invasive LR out of 25 cases, with a 153-month follow-up . In the present study, the LR is slightly higher (3/17), but the number of cases is lower and all LR occurred beyond 10 years.
These results are quite similar to DCIS treated by lumpectomy and WBRT in the series with a more than 120-month follow-up, both in retrospective studies and randomized trials [5,21-23]. However, it remains difficult to better identify the «aggressive» LCIS subtypes. A recent study by the Curie Insitute showed that KI67 should be used as a «discriminant» parameter to select more aggressive LCIS. Indeed, among 43 patients, the 5-year LR rates were 1/34 (3%) for low Ki 67 (≤10%) and 3/9 (33%) for high Ki 67 (>10%) (p = 0.0054) .
Another possible way of reducing the long-term risk of LR is the use of Tamoxifen. Indeed, the positivity rate of ER and/or PgR in LCIS is higher than in DCIS , and the results of the former NSABP P-1 prevention study showed that the most effective reduction of invasive BC by tamoxifen was observed among women with LCIS and ALH, suggesting a possible increased impact of anti-estrogens in the first steps of breast cancerization . Similar results were observed in the NSABP P-2 prevention trial (STAR) using Raloxifen . On the other hand, it should be remembered that the CBC rate in LCIS is quite higher than in DCIS, reaching 14% at 10 years in a large study from Connecticut tumor registry . Consequently, the use of tamoxifen should be considered, especially in pre-menopausal women with a lower incidence of thrombo-embolic accidents and uterine cancers.
Comparison between DCIS and LCIS (data adapted from references 1, 2, 5, 9, 13, 17, 36, 37)
Calcifications at diagnosis
Excision rate after CNB
Hormone receptor positivity
BCS + WBRT
10-year LR (after BCS)
The authors would like to thank Mrs Diane PENET for her translation skills.
- Venkitaraman R. Lobular neoplasia of the breast. Breast J. 2010;5:519–28.View ArticleGoogle Scholar
- Hussain M, Cunnick GH. Management of lobular carcinoma in situ and atypical lobular hyperplasia of the breast: a review. Eur J Surg Oncol. 2011;37:279–89.PubMedView ArticleGoogle Scholar
- King TA, Reis-Filho JS. Lobular Neoplasia. Surg Oncol Clin N Am. 2014;23:487–503.PubMedView ArticleGoogle Scholar
- Boyages J, Delaney G, Taylor R. Predictors of local recurrence after treatment of Ductal Carcinoma In Situ. A meta-analysis Cancer. 1999;85:616–28.PubMedGoogle Scholar
- Cutuli B, Bernier J, Poortmans P. Radiotherapy in DCIS, an underestimated benefit? Radiother Oncol. 2014;112:1–8.PubMedView ArticleGoogle Scholar
- Li C, Malone KE, Saltzman BS, Daling FR. Risk of invasive carcinoma among women diagnosed with ductal carcinoma in situ and lobular carcinoma in situ 1988–2001. Cancer. 2006;106:2104–12.PubMedView ArticleGoogle Scholar
- Marmor S, Portschy PR, Nzara R, Tuttle TM, Virnig BA. Trends in incidence and management of lobular carcinoma in situ: a population-based analysis. Ann Surg Oncol. 2013;20:3240–6.PubMedView ArticleGoogle Scholar
- Levi F, Te VC, Randimbison L, La Vecchia C. Trends of in situ carcinoma of the breast in Vaud, Switzerland. Eur J Cancer. 1997;33:903–6.PubMedView ArticleGoogle Scholar
- Oliveira TM, Elias JRJ, Melo AF, Teixeira SR, Filho SC, Goncalves LM, et al. Evolving concepts in breast lobular neoplasia and invasive lobular carcinoma, and their impact on imaging methods. Insight Imaging. 2014;5:183–94.View ArticleGoogle Scholar
- Rendi MH, Dintzis SM, Lehman CD, Calhoun KE, Allison KH. Lobular in-situ neoplasia on breast care needle. Biopsy: imaging indications and pathologic extent can identify which patients require excisional biopsy. Ann Surg Oncol. 2012;19:914–21.PubMedView ArticleGoogle Scholar
- Anderson BO, Calhoun KE, Rosen EL. Evolving concepts in the management of lobular neoplasia. J Natl Compr Cancer Netw. 2006;4:511–22.Google Scholar
- Bratthauer GL, Tavassoli FA. Lobular intraepithelial neoplasia: previously unexplored aspects assessed in 775 cases and their clinical implications. Vinchows Arch. 2002;440:134–8.View ArticleGoogle Scholar
- Lakhani SR, Audretsch W, Cleton-Jensen AM, Cutuli B, Ellis I, Eusebi V, et al. The management of lobular carcinoma in situ (LCIS). Is LCIS the same as ductal carcinoma in situ (DCIS)? Eur J Cancer. 2006;42:2205–11.PubMedView ArticleGoogle Scholar
- Lewis JL, Lee DY, Tartter PI. The significance of lobular carcinoma in situ and atypical hyperplasia of the breast. Ann Surg Oncol. 2012;19:4124–8.PubMedView ArticleGoogle Scholar
- Murray MP, Luedtke C, Liberman L, Nehhozina T, Akram M, Brogi E. Classic lobular carcinoma in situ and atypical lobular hyperplasia at percutaneous breast care biopsy. Outcomes of prospective excision. Cancer. 2013;119:1073–9.PubMedView ArticleGoogle Scholar
- Zhao C, Desouki MM, Florea A, Mohammed K, Li X, Dabbs D. Pathologic findings of follow-up surgical excision for lobular neoplasia on breast care biopsy performed for calcification. Am J Clin Pathol. 2012;138:72–8.PubMedView ArticleGoogle Scholar
- Bleicher RJ. Ductal carcinoma in situ. Surg Clin N Am. 2013;93:393–410.PubMedView ArticleGoogle Scholar
- Mokbel K, Cutuli B. Heterogeneity of ductal carcinoma in situ and its effects on management. Lancet Oncol. 2006;7:756–65.PubMedView ArticleGoogle Scholar
- Schouten Van Der Velden AP, Van Vugt R, Van Duck JA, Leer JW, Wobbes T. Local recurrences after different treatement strategies for ductal carcinoma in situ of the breast: a population-based study in the east Netherlands. Int J Radiat Oncol Biol Phys. 2007;69:703–10.PubMedView ArticleGoogle Scholar
- Tunon De Lara C, Andre G, Mac Grogan G, Dilhuydy JM, Bussieres JE, Debled M, et al. Ductal carcinoma in situ of the Breast: influence of age on diagnostic, therapeutic and prognostic features. Retrospective study of 812 patients. Ann Surg Oncol. 2011;18:1372–9.PubMedView ArticleGoogle Scholar
- Wapnir IL, Dignam JJ, Fisher B, Mamounas EP, Anderson SJ, Julian TB, et al. Long-term outcomes of invasive ipsilateral breast tumor recurrences after lumpectomy in NSABP B-17 and B-24 randomized clinical trials for DCIS. J Natl Cancer Inst. 2011;103:478–88.PubMed CentralPubMedView ArticleGoogle Scholar
- Donker M, Litiere S, Werutski G, Julien JP, Fentiman IS, Agresti R, et al. Breast-conserving treatment with or without radiotherapy in ductal carcinoma in situ: 15-year recurrence rates and outcomes after a recurrence rates and outcome after a recurrence, from EORTC 10583 randomized phase III trial. J Clin Oncol. 2013;31:4054–9.PubMedView ArticleGoogle Scholar
- Holmberg L, Garmo H, Grandstrand B, Ringberg A, Arnesson LG, Sandelin K, et al. Absolute risk reductions for local recurrence after postoperative radiotherapy after sector resection for Ductal Carcinoma in situ of the Breast. J Clin Oncol. 2008;26:1247–52.PubMedView ArticleGoogle Scholar
- Cuzick J, Sestak I, Pinder SE, Ellis IO, Forsyth S, Bundered NJ, et al. Effect of Tamoxifen and radiotherapy in women with locally excised ductal carcinoma in situ: long-term results of from the UK/ANZ DCIS trial. Lancet Oncol. 2011;12:21–9.PubMedView ArticleGoogle Scholar
- Early Breast Cancer Trialists’ Collaborative Group [EBCTCG], Correa C, MC Gale P, Taulor C, Wang Y, Clarke M, et al. Overview of the randomized trial of radiotherapy in ductal carcinoma in situ of the breast. J Natl Cancer Inst Monog. 2010;41:162–77.View ArticleGoogle Scholar
- Alvarado R, Lari SA, Roses RE, Smith BD, Yang W, Mittendorf EA, et al. Biology treatment and outcome in very young and older women with DCIS. Ann Surg Oncol. 2012;19:3777–84.PubMedView ArticleGoogle Scholar
- Halasz LM, Sreedhara M, Chen YH, Bellon JR, Punglia RS, Wong J, et al. Improved outcomes of breast-conserving therapy for patients with ductal carcinoma in situ. Int J Rad Oncol Biol Phys. 2012;82:e581-6.View ArticleGoogle Scholar
- Falk RS, Hofvind S, Skaane P, Haldorsen T. Second events following ductal carcinoma in situ of the breast: a register-based cohort study. Breast Cancer Res Treat. 2011;129:929–38.PubMedView ArticleGoogle Scholar
- Mccormick B, Winter C, Hudis C, Kuerer HM, Rakovitch E, Smith BL, et al. RTOG 9804: a prospective randomized trial for good-risk ductal carcinoma in situ comparing radiotherapy with observation. J Clin Oncol. 2015;33:709–15.PubMedView ArticleGoogle Scholar
- Kerlikowske K, Molinaro AM, Gauthier ML, Berman HK, Waldman F, Bennington F, et al. Biomarker expression and risk of subsequent tumors after initial ductal carcinoma in situ diagnosis. J Natl Cancer Inst. 2010;102:627–37.PubMed CentralPubMedView ArticleGoogle Scholar
- Rakovitch E, Narod SA, Nofech-Moses S, Hanna W, Thiruchelvam D, Saskin R, et al. Impact of boost radiation in the treatment of ductal carcinoma in situ: a population-based analysis. Int J Rad Oncol Biol Phys. 2013;86:491–7.View ArticleGoogle Scholar
- Cutuli B, Lemanski C, Le Blanc-Onfroy M, De Lafontan B, Cohen-Solal-Lenir C, Fondrinier E, et al. Local recurrence after ductal carcinoma in situ breast conserving treatment. Analysis of 195 cases. Cancer-Radiotherapie. 2013;17:196–201.PubMedView ArticleGoogle Scholar
- Salvadori B, Bartoli C, Zurrida S, Delledonne V, Squicciarini P, Rovini D, et al. Risk of invasive cancer in women with lobular carcinoma in situ of the breast. Eur J Cancer. 1991;27:35–7.PubMedView ArticleGoogle Scholar
- Ottesen GL, Graversen HP, Blichert-Toft M, Zedeler K, Andersen JA. Lobular carcinoma in situ of the female breast. Short-term results of a prospective nationwide study. The Danish Breast Cancer Cooperative Group. Am J Surg Pathol. 1993;17:14–21.PubMedView ArticleGoogle Scholar
- Fisher ER, Land SR, Fisher B, Mamounas E, Gilarski L, Wolmark N. Pathologic findings from the National Surgical Adjuvant Breast and Bowel Project twelve-year observations concerning lobular carcinoma in situ. Cancer. 2004;100:234–44.View ArticleGoogle Scholar
- Chuba PJ, Hamre MR, YAP J, Severson RK, Lucas D, Shamsa F, et al. Bilateral risk for subsequent breast cancer after lobular carcinoma in situ: analysis of surveillance. Epidemiology and End Results data. J Clin Oncol. 2005;23:5534–41.PubMedView ArticleGoogle Scholar
- Hughes LL, Wang M, Page DL, Gray R, Solin LJ, Davidson NE, et al. Local excision alone without irradiation for ductal carcinoma in situ of the breast: a trial of the Eastern Cooperative Oncology Group. J Clin Oncol. 2009;27:5319–24.PubMed CentralPubMedView ArticleGoogle Scholar
- Cutuli B, DE Lafontan B, Quetin P, Mery E. Breast conserving surgery and radiotherapy a possible treatment for lobular carcinoma in situ ? Eur J Cancer. 2005;41:380–5.PubMedView ArticleGoogle Scholar
- Vincent-Salmon A, Hajage D, Rouquette A, Cedenot A, Gruel N, Alran S, et al. High Ki67 expression is a risk marker of invasive relapse for classical lobular carcinoma in situ patients. Breast. 2012;21:380–3.View ArticleGoogle Scholar
- Fisher B, Costantino JP, Wickerham DL, Redmond CK, Kavanah H, Cronin WM, et al. Tamoxifen for prevention of breast cancer: report of the National Surgical Adjuvant Breast and Bowel Project P-1 Study. J Natl Cancer Inst. 1998;90:1371–88.PubMedView ArticleGoogle Scholar
- Vogel VG, Costantino JP, Wickerham DL, Cronin WM, Cecchini RS, Atkins JN, et al. Effects of tamoxifen vs raloxifen on the risk of developing invasive breast cancer and other disease outcomes: the NSABP Study of tamoxifen and raloxifen (STAR) P-2 trial. JAMA. 2006;295:2727–41.PubMedView ArticleGoogle Scholar
- Claus E, Stowe M, Carter D, Holford T. The risk of contralateral breast cancer among women diagnosed with ductal and lobular breast carcinoma in situ: data from Connecticut Tumor Registry. Breast. 2003;12:451–6.PubMedView ArticleGoogle Scholar
- Recht A. Should patients with lobular carcinoma in situ be irradiated? Not yet, but. Eur J Cancer. 2005;41:344–5.PubMedView ArticleGoogle Scholar
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