2016 ASCO conference | LOBULAR related Abstracts

JohnSmith

The annual ASCO (American Society of Clinical Oncology) conference starts in early June.
3-7 June 2016 - Chicago, Illinois, USA

Like the annual SABCS conference in December, ASCO is a very important meeting for Breast Cancer Oncologists.
The five-day event provides a venue for physicians and scientists to present research results to a global audience of oncology professionals. Clinical trial results and updates presented at the Annual meeting represent the extent of progress made each year in the fight against cancer.

This years program revealed 7 Abstracts dedicated to ILC.
By comparison, last years 2015 SABCS (which focuses on breast cancer) had only 10 sessions about ILC.

Below are the 7 ILC topics, followed by more details.

1. Pleomorphic invasive lobular breast carcinoma: Prognosis and characteristics compared with classical invasive lobular breast carcinoma.
2. Eight years retrospective analysis of the racial differences in hormone receptor status in lobular carcinoma of the breast in a community cancer center.
3. Outcomes of invasive ductal (ID) or invasive lobular (IL) early stage breast cancer in women treated with anastrozole or exemestane in the Canadian cancer trials Group MA.27.
4. Management of lobular carcinoma in situ: A decision analysis.
5. Clinicopathological characteristics and treatment outcomes in patients with stage I-III invasive lobular carcinoma of the breast (ILC) treated at the National Cancer Centre Singapore.
6. Cut-off analysis and prognostic relevance of Ki67 for resected early stage pure invasive lobular breast carcinoma (ILC).
7. Breast cancer histology and non-sentinel lymph node involvement following a positive sentinel lymph node biopsy: A multi-institutional cohort study.

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1. TITLE: Pleomorphic invasive Lobular breast carcinoma: Prognosis and characteristics compared with classical invasive lobular breast carcinoma.

Sub-category: Epidemiology
Category: Cancer Prevention, Hereditary Genetics, and Epidemiology
Meeting: 2016 ASCO Annual Meeting
Abstract No: e13094
Citation: J Clin Oncol 34, 2016 (suppl; abstr e13094)

Author(s): Christine H. Choi, Ying Liu, Kevin Kalinsky, Eileen Connolly;
Columbia University, New York, NY; Columbia University Medical Center, New York, NY

ABSTRACT:
Background: Pleomorphic lobular carcinoma (PLC) is a rare type of invasive lobular breast carcinoma that has traditionally been thought to have a worse prognosis as compared to classical lobular carcinoma (cILC), but prior studies are small with conflicting results. We seek to examine differences in clinical characteristics and progression-free and overall survival between PLC and cILC to guide treatment decisions.
Methods: From retrospective review of all women with invasive breast carcinoma seeking care at a single institution from 1998-2012, 146 women with PLC and 262 women with cILC were identified. Analysis was performed to examine differences in clinicopathologic variables and progression-free and overall survival between the two groups.
Results: On average, the PLC group had a significantly higher pathological stage, prevalence of lymphovascular invasion, proportion of node positive disease and proportion of mastectomy as compared to lumpectomy. There were no differences in age at diagnosis, tumor size, or mean number of positive nodes. Differences in race, subtype, grade, chemotherapy, hormonal therapy and radiation therapy were difficult to assess between the two groups as the cILC group had a higher proportion of missing data in those categories. On survival analysis, median follow-up was 60 months. In the PLC group there were 30 recurrences (21%), and in the cILC group there were 40 recurrences (15%), (chi-square p-value 0.175), as defined by STEEP criteria with the exception of death. In the PLC group, there were 27 deaths from all causes (18%), and in the cILC group there were 56 deaths from all causes (21%), (chi-square p-value 0.477). Results of multivariate cox proportional hazards models are ongoing.
Conclusions: In this largest cohort of women in the literature with PLC as compared to cILC, although the PLC group had some high risk clinicopathologic characteristics, there were no differences in rates of recurrences or death.
SOURCE: http://abstract.asco.org/176/AbstView_176_165663.h...

2. TITLE: Eight years retrospective analysis of the racial differences in hormone receptor status in Lobular carcinoma of the breast in a community cancer center.

Sub-category: HER2+
Category: Breast Cancer—HER2/ER
Meeting: 2016 ASCO Annual Meeting
Abstract No: e12069
Citation: J Clin Oncol 34, 2016 (suppl; abstr e12069)

Author(s): Jean Gabriel Bustamante Alvarez, Jessica Stemple, Konstantinos Sdrimas, Nellowe Candelario, Alessandro Bombonati, Supakanya Wongrakpanich, Aristides Telonis;
Albert Einstein Medical Center, Philadelphia, PA; Einstein Medical Center, Philadelphia, PA; Thomas Jefferson University Hospital, Philadelphia, PA

Abstract:
Background: Estrogen receptor (ER) positivity in breast tumors has a beneficial prognostic profile. However, ER-positive and progesterone receptor (PR) negative tumors have a higher relative risk of mortality, as well as ER-negative/PR-positive and ER-negative/PR-negative tumors. HER 2/neu, when overexpressed, confers aggressive behavior to breast cancers. Ethnic differences between hormone receptor positivity in lobular breast carcinoma have not yet been fully described.
Methods: We retrospectively ascertained patients at AEMC between 2003 and 2011 with lobular breast carcinoma by review of medical records. Age of diagnosis according with Her2, ER and PR positivity were evaluated with a student T-test, as well as according to race (African American vs. Non-Hispanic whites). We also assessed differences of hormone receptor positivity (ER/PR) and Her2/Neu between African Americans and Non-Hispanic whites with a Chi square test.
Results: 143 cases were included. 84 patients were Non-Hispanic whites with lobular breast carcinoma, of which 4.76 % were Her2/neu-positive, 97.61 % were ER-positive, and 77.38% were PR-positive. From a total of 59 African Americans, 3.38% were Her2-positive, 98.30% ER-positive, and 74.57% PR-positive. No difference was found in the median age of diagnosis (67 years) among ethnic groups p=0.960 (p>0.05) or according to Her2/neu, ER or PR positivity (p=0.684, 0.5 and 0.23, respectively). ER positivity was more prevalent in Non-Hispanic Whites p=0.043 (p < 0.05). Her2/neu showed no difference in prevalence p=0.414. PR positivity was more frequent among the Non-Hispanic white population when compared with African Americans.
Conclusions: In this study, lobular carcinoma showed higher prevalence of ER and PR positivity in Non-Hispanic whites. There was no statistical significance regarding Her2/neu positivity or median age of diagnosis between ethnic groups. These findings suggest that Non-Hispanic whites with lobular breast carcinoma have a more favorable hormone receptor profile.
SOURCE: http://abstract.asco.org/176/AbstView_176_161918.h...

3. TITLE: Outcomes of invasive ductal (ID) or invasive Lobular (IL) early stage breast cancer in women treated with anastrozole or exemestane in the Canadian cancer trials Group MA.27.

Sub-category: ER+
Category: Breast Cancer—HER2/ER
Meeting: 2016 ASCO Annual Meeting
Abstract No: 521
Poster Board Number: Poster Discussion Session (Board #9)
Citation: J Clin Oncol 34, 2016 (suppl; abstr 521)

Author(s): Kathrin Strasser-Weippl, Gautam Sudan, Ravi Ramjeesingh, Lois E. Shepherd, Joyce O'Shaughnessy, Bingshu E. Chen, Wendy R. Parulekar, Pedro Emanuel Rubini Liedke, Paul E. Goss;
Wilheminen Hospital, Vienna, Austria; Canadian Cancer Trials Group, Queen's University, Kingston, ON, Canada; Nova Scotia Cancer Centre, Department of Medicine, Dalhousie University, Nova Scotia, NS, Canada; Canadian Cancer Trials Group, Kingston, ON, Canada; Baylor University Medical Center, Texas Oncology, Dallas, TX; NCIC Clinical Trials Group, Cancer Research Institute, Queen's University, Kingston, ON, Canada; Hospital De Clinicas de Porto Alegre, Porto Alegre RS, Brazil; Massachusetts General Hospital Cancer Center and Harvard Medical School, Boston, MA

Abstract:
Background: Previous data suggest histologic subtype, invasive ductal (ID) versus (vs) invasive lobular (IL), might be a marker for response to hormone therapy in receptor positive (HR+) breast cancer [Metzger O, et al: Cancer Res 2012, 72:S1-1].
Methods: MA.27 compared five years of adjuvant anastrozole (A) or exemestane (E) in patients with HR+ early breast cancer. We evaluated ID versus IL histology (based on original pathology reports) as a prognostic marker for outcomes.
Results: We were able to include 5,709 patients (5,021 with ID and 688 with IL histology, out of 7,576 patients in MA.27) who had a median follow-up of 4.1 years. Histologic subtype did not influence overall survival (OS) or event-free survival (EFS) in the overall study cohort (HR 1.04, P = 0.81 and HR 1.14, P = 0.49, respectively). In univariable analysis of OS, there was no significant difference between treatment with E vs A in the ID group (HR = 0.92, P = 0.46). In the IL group, a marginally significant difference in favor of treatment with anastrozole was seen (HR = 1.79, P = 0.055). In multivariable analysis a prognostic effect of the interaction between treatment and histological subtype on OS (but not on EFS) was noted, suggesting a better outcome for patients with IL cancer when treated with anastrozole (HR 2.1, P = 0.05). After a stepwise selection process in the multivariable model, a marginally significant prognostic effect for the interaction variable (treatment with histological subtype) on OS (but not on EFS) was noted (Ratio of HR 2.1, P = 0.05).
Conclusions: Histologic subtype did not have an effect on OS or EFS in patients in MA.27. Neither A or E had a differential effect on IDC versus ILC with respect to EFS. However, similar to data from the BIG 1-98 trial, our data suggest an interaction effect between treatment and histology (P = 0.05) on OS. Here, patients with ILC had a better OS when treated with A vs E (HR 1.79, P = 0.055), whereas no difference was noted for patients with IDC (HR 0.92, P = 0.47).
SOURCE: http://abstract.asco.org/176/AbstView_176_165026.h...

4. TITLE: Management of Lobular carcinoma in situ: A decision analysis.

Sub-category: Local Therapy
Category: Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Meeting: 2016 ASCO Annual Meeting
Abstract No: 1048
Poster Board Number: Poster Session (Board #153)
Citation: J Clin Oncol 34, 2016 (suppl; abstr 1048)

Author(s): Stephanie M Wong, Natasha K. Stout, Rinaa S. Punglia, Mehra Golshan;
McGill University Health Centre, Montreal, QC, Canada; Harvard Medical School and Harvard Pilgrim Health Care Institute, Boston, MA; Dana-Farber Cancer Institute, Boston, MA; Brigham and Women's Hospital/Dana-Farber Cancer Institute, Boston, MA

Abstract:
Background: Women diagnosed with LCIS have a three to ten-fold increased risk of developing invasive breast cancer, and controversy remains regarding the best strategy for management of this diagnosis. We sought to evaluate the life expectancy and survival differences offered by active surveillance, risk-reducing chemoprevention, and bilateral prophylactic mastectomy (BPM).
Methods: We constructed a Markov simulation model to determine life expectancy (LE) gains and survival for hypothetical cohorts of women diagnosed with LCIS at age of 40, 50 and 60 under alternative risk-reduction strategies. Probabilities for invasive breast cancer, breast cancer-specific mortality, effectiveness of preventive strategies and complication rates were derived from published studies and the Surveillance, Epidemiology and End Results database. Sensitivity analyses were performed to evaluate the stability of results to changes in model parameters.
Results: Assuming a breast cancer incidence of 1-2% per year under active surveillance, a 50-year-old woman diagnosed with LCIS would have a total LE of 31.6-32.3 years, and would gain 0.32-0.64 years in LE by adding chemoprevention and 0.70-1.28 years by BPM. In our model, the largest gains were seen in young women aged 40-years at diagnosis, while increasing age at diagnosis attenuated gains associated with active prevention strategies. Ten-year overall survival (OS) with active surveillance ranged from 96.1-97% if diagnosed at 40-years, 93.6-94.5% at 50-years, and 88.5-89.3% at 60-years. Absolute percent differences in overall survival ranged from 0.5-1.1% with chemoprevention and 0.7-1.7% with BPM.
Conclusions: Among women with a diagnosis of LCIS, LE gains were seen for risk-reducing strategies such as chemoprevention and BPM, particularly in younger women. Coupled with information about the potential side effects associated with each management strategy, these results may be useful to help guide women and their physicians in the decision making process.
SOURCE: http://abstract.asco.org/176/AbstView_176_165127.h...

5. TITLE: Clinicopathological characteristics and treatment outcomes in patients with stage I-III invasive Lobular carcinoma of the breast (ILC) treated at the National Cancer Centre Singapore.

Sub-category: ER+
Category: Breast Cancer—HER2/ER
Meeting: 2016 ASCO Annual Meeting
Abstract No: e12005
Citation: J Clin Oncol 34, 2016 (suppl; abstr e12005)

Author(s): Joycelyn Jie Xin Lee, Fuh-Yong Wong, Benita Tan, Swee Ho Lim, Sze Huey Tan, Joanne YY Ngeow, Rebecca Alexandra Dent;
Department of Medical Oncology, National Cancer Centre Singapore, Singapore, Singapore; Department of Radiation Oncology, National Cancer Centre Singapore, Singapore, Singapore; Department of General Surgery, Singapore General Hospital, Singapore, Singapore; Breast Department, KK Women's and Children's Hospital, Singapore, Singapore; Division of Clinical Trials and Epidemiological Sciences, National Cancer Centre Singapore, Singapore, Singapore; National Cancer Center Singapore, Singapore, Singapore

Abstract:
Background: Increasing evidence suggests that ILC differs from invasive ductal carcinoma (IDC) but even within ILC there is significant heterogeneity. We aim to identify prognostic factors in our cohort of ILC patients (pts).
Methods: 371 pts with stage I-III ILC diagnosed between October 1991 and May 2015 were included. Cox regression analysis was used to evaluate the association between clinicopathological characteristics, treatment received and survival outcomes.
Results: Median age at diagnosis was 54 years (range 33.8-84.9) and most pts were Chinese (77%). 204 (69%) of tumors were ER+/PR+/HER2-, 56 (19%) ER+/PR-/HER2-, 20 (7%) ERany/PRany/HER2+, and 17 (5%) ER-/PR-/HER2- (triple negative). 150 (40.4%) had stage I disease, 114 (30.7%) stage II disease and 107 (28.8%) had stage III disease. 242 pts (65%) had a mastectomy while 129 (35%) had breast conserving surgery. 159 (43%) received chemotherapy (24 as neoadjuvant, 135 as adjuvant), 236 (64%) adjuvant radiotherapy and 306 (82%) adjuvant hormonal therapy. Median overall survival (OS) was 17 years (95% CI 14.3–not estimable). In multivariable analysis, in addition to TNM staging, pts with screen-detected cancers were also shown to have significantly better disease-free survival (DFS) (HR 0.47, 95% CI 0.230–0.975) and OS (HR 0.09, 95% CI 0.012–0.655) compared to those with clinically-detected cancers.
Prior use of oral contraceptives (OCP) was also associated with improved DFS (HR 0.22, 95% CI 0.081–0.620) and OS (HR 0.10, 95% CI 0.014–0.744).
Among 306 pts who had adjuvant endocrine therapy, 222 (73%) used tamoxifen while 82 used other hormonal options. Use of tamoxifen was associated with a poorer DFS compared to other hormonal adjuvants (HR 2.18, 95% CI 0.936–5.066) although this did not reach statistical significance (p = 0.07).
Conclusions: ILC are heterogenous in their clinicopathological characteristics and survival outcomes. Interval cancers are associated with a worse prognosis while OCP use is associated with better survival, though our study is limited by cohort size. Future studies should evaluate molecular heterogeneity to help us better tailor treatment choices.
SOURCE: http://abstract.asco.org/176/AbstView_176_163050.h...

6. TITLE: Cut-off analysis and prognostic relevance of Ki67 for resected early stage pure invasive Lobular breast carcinoma (ILC).

Sub-category: ER+
Category: Breast Cancer—HER2/ER
Meeting: 2016 ASCO Annual Meeting
Abstract No: 544
Poster Board Number: Poster Session (Board #32)
Citation: J Clin Oncol 34, 2016 (suppl; abstr 544)

Author(s): Luisa Carbognin, Isabella Sperduti, Maria Vittoria Dieci, Gaia Griguolo, Valentina Guarneri, Matteo Brunelli, Lisa Marcolini, Enrico Orvieto, Rolando Nortilli, Sara Pilotto, Elisa Filippi, Elena Fiorio, Erminia Manfrin, Francesca Pellini, Franco Bonetti, Giovanni Paolo Pollini, Pier Franco Conte, Giampaolo Tortora, Emilio Bria;
University of Verona, Verona, Italy; Bio-Statistics Unit Regina Elena National Cancer Institute, Italy, Rome, Italy; University of Padova and Istituto Oncologico Veneto IOV IRCCS, Padova, Italy; U.O. Oncologia Medica 2, Istituto Oncologico Veneto - IRCCS, Padova, Italy; Department of Pathology and Diagnostic, Azienda Ospedaliera Universitaria Integrata (AOUI) and University of Verona, Italy, Verona, Italy; Department of Pathology and Diagnostic, University of Verona, Verona, Italy; Azienda Ospedaliera di Padova, Padova, Italy; Medical Oncology, University of Verona, Verona, Italy; Breast Unit, Azienda Ospedaliera Universitaria Integrata, Verona, Italy; UOC Oncologia Medica, AOUI , Verona, Italy; Pathology d.U, AOUI, Verona, Italy; Department of Surgery, University of Verona, Verona, Italy; Surgery d.U, AOUI, Verona, Italy; Instituto Oncologico Veneto, IOV-IRCCS, Padova, Italy; Azienda Ospedaliera Universitaria Integrata, University of Verona, Verona, Italy

Abstract:
Background: In clinical practice, the prognostic potential (and best cut-off) of Ki67 for pure ILC is usually borrowed from the ductal histotype, though a formal validation has not yet been fully established. Thus, the aim of this analysis was to investigate the best prognostic cut-off value of Ki67 and its long-term impact assay in a multi-center series of patients affected by early stage pure ILC.
Methods: Clinical-pathological data of consecutive patients affected by pure ILC undergone surgery between January 1990 and December 2013, diagnosed at 2 Italian institutions, were retrospectively correlated with overall survival and disease-free survival (OS/DFS) using a Cox model. The maximally selected Log-Rank statistics analysis was applied to the Ki67 continuous variable to estimate the appropriate cut-off. Kaplan-Meier curves were compared with Log-Rank analysis. Internal cross-validation was accomplished.
Results: Data from 457 pts were gathered (median age 61 years [yrs], range 35-96 yrs). At median follow-up of 75 months, 5-/10-years DFS and OS were 82.5%/71.4% and 91.8%/81.7%, respectively. The maximally selected Log-Rank statistics analysis identified 4% as optimal cut-offs for OS. Ki67 (HR 2.28, 95% CI 1.0-5.19, p=0.05), ECOG Performance Status (PS) (HR 3.27, 95% CI 1.49-7.18, p=0.003), lymph-node status (HR 2.96, 95% CI 1.53-5.74, p=0.001), and tumor-size according to TNM (HR 2.6, 95% CI 1.31-5.13, p=0.006) were independent predictors for OS at the multivariate analysis. Log-rank analysis is shown in the table. Ki67 highly replicated at the internal cross-validation analysis. PS (HR 3.73, 95% CI 1.50-9.30, p=0.005) and lymph-node status (HR 3.75, 95% CI 1.70-8.26, p=0.001) were independent predictors for DFS.
Conclusions: Despite the retrospective and exploratory nature of the study, a very low cut-off of Ki67 (4%) was able to significantly discriminate the prognosis of patients with ILC.
SOURCE: http://abstract.asco.org/176/AbstView_176_167028.h...

7. TITLE: Breast cancer histology and non-sentinel lymph node involvement following a positive sentinel lymph node biopsy: A multi-institutional cohort study.

Sub-category: Local Therapy
Category: Breast Cancer—Triple-Negative/Cytotoxics/Local Therapy
Meeting: 2016 ASCO Annual Meeting
Abstract No: 1043
Poster Board Number: Poster Session (Board #148)
Citation: J Clin Oncol 34, 2016 (suppl; abstr 1043)

Author(s): Alana Hosein, Dominique LeBlanc, Amanda Roberts, Erin Cordeiro, Sharon Nofech-Mozes, Bruce Youngson, David R. McCready, Manar Al-Assi, Stephanie Ramkumar, Tulin Cil;
Department of Surgery, University of Toronto, Toronto, ON, Canada; University Health Network, Toronto, Ontario, Canada; The Ottawa Hospital, Ottawa, ON, Canada; Sunnybrook Health Sciences Centre, Department of Pathology, Toronto, ON, Canada; University Health Network, Toronto, ON, Canada; Princess Margaret Hospital, Toronto, ON, Canada; Department of Anatomic Pathology, Sunnybrook Health Sciences Centre, Toronto, ON, Canada; Division of General Surgery, University of Toronto, Toronto, ON, Canada; University of Toronto, Toronto, ON, Canada

Abstract:
Background: Management of the axilla in early breast cancer has shifted towards a more conservative surgical approach. The omission of a completion axillary lymph node dissection (cALND) in the context of a positive sentinel lymph node (SLN) has become common, even though this practice may result in residual non-sentinel positive nodes left behind. Furthermore, the axillary management of both invasive ductal and invasive lobular carcinomas (IDCs and ILCs) has traditionally been the same despite the different pattern of invasion and metastases in ILCs. The objective of this study was to determine if lobular histology is an independent predictor of non-sentinel lymph node (NSLN) involvement following a positive SLN biopsy (SLNB).
Methods: A multi-institutional cohort study was completed. Patients with node positive IDC or ILC who were treated with both a SLNB followed by cALND from November 1997 to June 2009 were included. The primary outcome was NSLN involvement, defined as having at least one positive lymph node within the cALND specimen. Univariate analysis was performed to determine baseline differences between the IDC and ILC subgroups. A multivariable logistic regression analysis was performed to determine the independent effect of lobular histology on NSLN involvement.
Results: A total of 261 cALNDs from 259 patients were included. The primary histology was ductal for 200 (77%) of the tumors. Overall, 35.6% of all cALNDs had NSLNs involved. The presence of lymphovascular invasion (LVI) within the primary tumor (OR 3.28, p = 0.0009) and the absolute number of SLNs involved (OR 2.54, p < 0.0001) were both found to be independent predictors of NSLN involvement. Lobular histology was not an independent predictor (OR 1.42, p = 0.42).
Conclusions: Within our cohort, Lobular histology is not an independent predictor of residual disease in NSLNs. Predictors of nodal involvement included presence of LVI and the absolute number of positive SLNs. Overall, the clinical practice changes to axillary management following a positive SLN biopsy appear to be generalizable to both ductal and lobular breast cancers.
SOURCE: http://abstract.asco.org/176/AbstView_176_163612.h...

* NOTE: There were seven additional abstracts that mention the word "Lobular" but were not focused on ILC:
These included:

• Checking HER2 rates in breast cancer: A 4 year-experience with a nationwide database containing 105,717 records—HER-France.
• Use of the 21 gene recurrence score (RS) assay results in patients (pts) treated with intraoperative radiation therapy (IORT) for early stage (ES) breast cancer.
• Comparative performance of surveillance mammography and breast MRI in women with a history of breast cancer.
• Use of serial 18F-Fluorothymidine (FLT) PET and Ki-67 to predict response to Aromatase Inhibitors (AI) in women with ER+ breast cancer.
• Value of mitotic index in residual tumors following neoadjuvant therapy for breast cancer: Single institution experience.
• Biomarkers of immune checkpoint inhibitor response in metastatic breast cancer: PD-L1 protein expression, CD274 gene amplification, and total mutational burden.
• Phase II trial of Neratinib for HER2 mutated, non-amplified metastatic breast cancer (HER2mut MBC).

Optimist52

Thanks John, reading the abstract conclusion about PILC is somewhat reassuring to me as I have this subtype. It's wonderful to see that ILC is being researched more.

Sunnyone22

As always - thanks, John, for your vigilance of ILC studies. You make it so much easier for those of us who are not so scientifically oriented to learn the latest.

robin_in_SJ

Thanks, John. It was good to see some research on PLC vs cLC, it's been hard to find information on treatment outcomes and survival comparisons.

dAd

Thank you so much for this John. Really interesting information for those of us with ILC.

JohnSmith

This is not related to the ASCO conference (which starts this week), but it's a new ILC paper and worth adding to this thread.
Published May 2016.

Lobular breast cancer: Clinical, molecular and morphological characteristics.
Christgen M1, Steinemann D2, Kühnle E3, Länger F4, Gluz O5, Harbeck N6, Kreipe H4.
Author info:
1Institute of Pathology, Hannover Medical School, Hannover, Germany. Email: Christgen DOT Matthias AT MH-Hannover.de
2Institute of Human Genetics, Hannover Medical School, Hannover, Germany.
3Department of Gynecology and Obstetrics, Hannover Medical School, Hannover, Germany.
4Institute of Pathology, Hannover Medical School, Hannover, Germany.
5Evangelic Bethesda Hospital, Breast Center Niederrhein, Moenchengladbach, Germany; West German Study Group, Moenchengladbach, Germany.
6West German Study Group, Moenchengladbach, Germany; Breast Center, University of Munich (LMU), Munich, Germany.

Abstract
Infiltrating lobular breast cancer (ILBC) is the most common special breast cancer subtype. This review provides a comprehensive description of ILBC characteristics, including epidemiology, clinical features, molecular genetics and histomorphology. Twenty detailed supplemental data tables guide through primary data of more than 200 original studies. Meta-analyses indicate that ILBC is at least twice as common in the Western world as it is in other geographic regions. ILBC is over-represented in so-called interval carcinomas and in primary metastatic breast cancer. ILBC is also associated higher age, higher pT stage and hormone receptor (ER/PR) positivity. Pathological complete response rates after neoadjuvant chemotherapy are low, ranging between 0% and 11%. Positive resection margins after breast-conserving surgery are comparatively frequent and 17% to 65% of patients undergo a second surgical intervention. Depending on the morphological stringency in the diagnosis of ILBC, lack of E-cadherin expression is observed in 55% to 100% of cases. CDH1/E-cadherin mutation detection rates vary between 12% and 83%. Various additional molecular factors, including PIK3CA, TP53, FOXA1, FGFR1, ZNF703 and BCAR4, have been implicated in ILBC or progression of lobular carcinoma in situ (LCIS) to invasive cancer and are discussed in detail. Eight instructive figure plates recapitulate the histomorphology of ILBC and its variants. Furthermore, we draw attention to rarely addressed histological details, such as two-sided nuclear compression and fat-avoiding growth at the invasion front. Last but not least, we discuss future translational research directions and emphasize the concept of synthetic lethality, which promises new options for targeted ILBC therapy.