Review and Progress

The Diagnosis and Treatment of Breast Invasive Lobular Carcinoma  

Li W.Q.1 , Zhai Z.W.1 , Guo Z.F.1 , Zhang D.W.1,2
1 The Second Hospital of Harbin Medical University, Harbin, 150081, China
2 Heilongjiang Academy of Medical Sciences, Harbin, 150081, China
Author    Correspondence author
Cancer Genetics and Epigenetics, 2017, Vol. 5, No. 1   doi: 10.5376/cge.2017.05.0001
Received: 04 Jan., 2017    Accepted: 05 Jan., 2017    Published: 05 Jan., 2017
© 2017 BioPublisher Publishing Platform
This is an open access article published under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Preferred citation for this article:

Li W.Q., Zhai Z.W., Guo Z.F., and Zhang D.W., 2017, The diagnosis and treatment of breast invasive lobular carcinoma, Cancer Genetics and Epigenetics, 5(1): 1-5 (doi: 10.5376/cge.2017.05.0001)


Invasive lobular carcinoma of the breast to breast cancer cells in the breakthrough of mammary gland flocculus endings tube or to lobular acini basement membrane mesenchymal invasive growth as the main characteristics.Breast invasive lobular carcinoma usually has a better prognosis of phenotype, low-level histological grade, low  mitotic index, hormone receptor-positive,its her-2 negative, P53, low, lack of calcium mucin, sensitivity to endocrine therapy.Tended to be older patients diagnosis, tumor larger, axillary lymph node metastasis rate is higher, when a side breast invasive lobular carcinoma, the contralateral tend to occur.Invasive lobular carcinoma invasive is strong, has extensive transfer value tendency, therefore, in some studies in comparison with other invasive carcinoma with poor prognosis.

Invasive lobular carcinoma; Immunohistochemistry and molecular biology; Comprehensive treatmen

ILC usually shows the unique morphology,pathology and molecular,and the tend of the incedence is increasing year by year. Breast invasive lobular carcinoma was reviewed in this article, in which including the clinical manifestation, auxiliary examination, pathological characteristics, molecular, comprehensive treatment, the latest progress of these sides.



Breast cancer is a heterogeneous disease, which has more than 30 kinds of tissue types. The infiltrating ductal carcinoma (invasive ductal carcinoma, IDC) accounted for 60% 70%, invasive lobular carcinoma is the second common type of invasive cancer, 5% ~ 15% (Reed et al., 2015). of the invasive breast cancer , just less than the infiltrating ductal carcinoma. The peaks of the Invasive lobular carcinoma is in 50 ~ 60 postmenopausal women, the infiltrating ductal carcinoma is higher 1 ~ 3 years old on average, and some patients are under 40 years old (Oliveira et al., 2014).


Clinical Manifestation

The clinical feature of invasive lobular carcinoma is specific bump, but sometimes which lack of clear boundary, and the bump is a little greater than patients with IDC. The bump of 5cm is common. Lymph nodes change: It is always late when the patients with tumor were found, and the lymph node metastasis rate is higher. Viscera metastas: The transfer ways of Invasive lobular carcinoma and infiltrating ductal carcinoma are different. The latter is common in the lung, liver and brain metastasis. Lobular carcinoma is easy to transfer to the surface of pia mater, peritoneal and retroperitoneal areas, such as the gastrointestinal tract, reproductive organs and bone (Li and Li, 2012).


Auxiliary Examination

Imaging change: Maybe diffuse invasive growth and the most of the type of glandular or high density mammary gland, Mammography in the diagnosis of ILC is often misdiagnosis. False negative rate is 10% higher than the infiltrating ductal carcinoma, sensitivity is 57% ~ 92%, and we underestimate the size of focus. The change of ILC in MRI is irregular lump, astral jagged edges, uneven reinforcement of mass, and there is no significant difference between the IDC in enhanced MRI. To evaluate the range and morphological characteristics of ILC, MRI is superior than X-ray examination, and its sensitivity is more than 90%, but in the role of preoperative analysis remains controversial. So, MRI is used to guide the preoperative of breast conserving surgery and assessment of potopeerative. Ultrasonic is a better imaging examination method to judge invasive lobular carcinoma, and the sensitivity is 68% to 68%.The patients with ILC can be found by ultrasonic, but the lesions can’t be found in the X (Menezes et al., 2013). The sonographic appearances of the ILC and IDC ultrasound are similar, irregular shape, and the ultrasound elastography can improve the detection rate.


Pathology Characteristics

Invasive lobular carcinoma macroscopic view: invasive lobular carcinoma’s cut is mostly gray with sclerosing and fibrous appearance, no bleeding, calcification and yellow-white stripe generally. Histology is characterized by the cancer cells into single line arrangement, or around the catheter and small lobe concentric circles sample arrangement, or a single scattered diffuse, in a fibrous stroma. The cells is of small size, uniform, lack of adhesion between each other, seldom produces a fibrous reaction. ILC has multicenter growth characteristics of multifocal, multicenter incidence is for 9% ~ 50%, 8% ~ 19% for double side (Sinn et al., 2014). Diversity (including multifocal, multicenter, diffuse, double side) incidence is 44.4%.


Immunohistochemical Characteristics

ILC cancer in estrogen receptor (ER) positive rate is about 90%, which is 70% ~ 80% higher than that of infiltrating ductal carcinoma, progesterone (PR) positive rate is 60% ~ 70% (Sikora et al., 2014). Her - 2 and P53 are usually lower expresses, and Her-2 positive expression rate is lower than that of IDC. Ki67 and mitotic index value are generally low (Dabbs et al., 2013). Another important phenotypic characteristics is that the lack expression of calcium in the E -cadherin. And the lack of E -cadherin may be associated with CDH 1 gene mutations (Petridis et al., 2014). E - cadherin is a transmembrane glycoprotein involved in cell adhesion, E - cadherin expressed weaken or disappear in ILC , E - cadherin in IDC is positive (Engstrøm et al., 2015). P120 also can be used in the identification of ILC and IDC,and the ILC p120 cytoplasmic is positive, positive capsule of p120, p120 has become one of the invasive lobular carcinoma immunohistochemical markers (Li et al., 2014).


Clinical Outcomes

The most important prognostic factors depends on the size of the tumor and lymph node metastasis. According to the grade of Nottingham, close to 76% invasive lobular carcinoma belongs to grade 2 (Rakha et al., 2013). Primary diagnosis with mass are less than 3 cm, regional lymph node negative, clinical pathologic stage for phase I, II, hormone receptor-positive, and endocrine therapy. Postoperative 5-year disease-free survival rate is higher. Invasive lobular carcinoma was found late, aggressive, with broad transfer and proliferation tendency, therefore, in some studies, in which compare with other invasive carcinoma with poor prognosis, whether for endocrine therapy may be the important indexes affecting the prognosis.


Comprehensive Treatment

Treatments include local lesion surgery, radiotherapy and endocrine therapy, biological to medication or by a combination of the above treatments application. Variety of treatment choices should be based on the tumor’s histological characteristics, clinical and pathological features of primary tumor, axillary lymph node status, tumor hormone receptor level, Her - 2 state, with or without detected the metastatic lesions, complications, patients' age, menopausal status, etc.



Surgery is one of the main treatments of breast cancer, there are many types of surgical procedure, including modified radical mastectomy, Unilateral mastectomy + sentinel lymph node biopsy, breast-conserving surgery, etc. Invasive lobular carcinoma’s breast-conserving surgery recurrence rate is higher, perhaps due to invasive lobular carcinoma is multifocal and centricity (Nounou et al., 2015). Surgical choice should minimize the surgical damage, and try our best to keep breast shape in patients with early breast cancer, but we must control strictly, in order to effect a radical cure which is given priority to, and keep the principle of function and appearance’s complementary.



Radiation treatment includes before or after operation for auxiliary radiation therapy, including radical palliative radiotherapy of advanced breast cancer. Indications: (1) the primary tumor maximum diameter is of 5 cm or more, or the tumor invades the breast skin or chest wall; (2) the axillary lymph node metastasis are 4 or more; (3) the lymph node metastasis is of 1 ~ 3 for T/T 2 1, the data also supports the value of postoperative radiotherapy. It contains at least one of the following factors .The patients are likely to be higher risk of recurrence, and postoperative radiotherapy is more meaningful: age 40 years old or older, or less number of cleaning axillary lymph node < 10, transfer rate > 20%, hormone receptor negative, its Her - 2 / neu expression, etc (Budach et al., 2015). For ILC, radiotherapy and infiltrating ductal carcinoma are same to IDC.


The Chemical Drugs

As an integral part of comprehensive treatment of breast cancer, the purpose of systemic chemotherapy is the eradication of residual tumor cells within the body, in order to improve the cure rate of surgery. Postoperative adjuvant chemotherapy of breast cancer improves disease-free survival in patients with breast cancer (DFS) and overall survival (OS) significantly. But in a retrospective study to evaluate the benefit of chemotherapy and the interaction between estrogen receptor status, proves that the ER negative breast cancer patients can benefit from chemotherapy more (Delpech et al., 2013).


Chemotherapy, 4 cycles of AC (doxorubicin and cyclophosphamide) is equivalent to 6 cycles of CMF, and 6 cycles of anthracycline chemotherapy has more advantages. Joining the paclitaxel can improve the curative effect of chemotherapy, anthracycline plus paclitaxel reduce a third of breast cancer mortality (Sonnenblick et al., 2015). More and more applied in patients with breast cancer, neoadjuvant chemotherapy will shrink tumors .So that it can be able to surgery in patients with locally advanced breast cancer, and it’s able to put patients who could not do brease-conserving surgery. For Her - 2 positive patients, before the application of targeted therapy, which should be chosen that is associated with paclitaxel of neoadjuvant chemotherapy, can increase the rate of pathologic complete response (Park et al., 2015). Invasive lobular carcinoma is not sensitive to neoadjuvant chemotherapy, and can’t increase the probability of breast-conserving surgery, studies have shown that the cut edge positive rate of ILC’s breast-conserving surgery is 16% higher than that of IDC (Braunstein et al., 2015).


Endocrine Therapy

Breast cancer, a kind of tumors, is closely related to the endocrine, as a result of the ILC immunohistochemical positive rate of ER and PR are obviously higher than that of other types of breast cancer, so the endocrine therapy appears especially important. At present, the endocrine therapies for breast cancer include anti-estrogen drugs such as tamoxifen (TAM), toremifene, aromatase inhibitors (AI) (letrozole, anastrozole, exemestane, etc.), progesterone (megestrol, medroxyprogesterone) and luteinizing hormone (LH - RH) release antagonists, Clinical treatment choice is the first and the second above all, and choosing the appropriate drugs should be based on patients’ menstrual state. General premenopausal patients preferred tamoxifen, oral tamoxifen 5-10 years, tamoxifen with thromboembolism, and endometrial cancer closely related (Christinat et al., 2013). The postmenopausal patients preferred the third generation of aromatase inhibitors, reach menopause state by drugs or surgery can also choose aromatase inhibitors (Davies et al., 2013). Recurrent metastatic breast cancer (MBC) endocrine therapy can choose fulvestrant.


The Molecular Targeted Drug Therapy

Molecular targeted drugs, a new treatment method is following the surgery, radiotherapy and chemotherapy after the three traditional modes. Targeted therapy mechanism utilizing the tumor cells can express, and the normal cells express specific genes or gene products little or not, maximize killing tumor cells molecular targeted drugs for the treatment of breast cancer are marketed, Trastuzumab, Pertuzumab, Lapatinib, bevacizumab, etc, are widely used in clinical practice. Pertuzumab add to Trastuzumab andpaclitaxel is the first-line treatment of metastatic breast cancer to Her - 2 positive patients (Swain et al., 2014).



This work was supported by the Science Innovation Project (201613) and Special Fund for Excellent Academic Leader of Harbin (2015RAXYJ051).



Budach W., Matuschek C., and Bölke E., 2015, Erratum to: DEGRO practical guidelines for radiotherapy of breast cancer V: Therapy for locally advanced and inflammatory breast cancer, as well as local therapy in cases with synchronous distant metastases, Strahlentherapie and Onkologie, 191(8): 623-633


Braunstein L.Z., Brock J.E., Chen Y.H., Truong L., Russo A.L., Arvold N.D., and Harris J.R., 2015, Invasive lobular carcinoma of the breast: local recurrence after breast-conserving therapy by subtype approximation and surgical margin, Breast Cancer Research and Treatment, 149(2): 555-564



Christinat A., Lascio S.D., and Pagani O., 2013, Hormonal therapies in young breast cancer patients: when, what and for how long?, Journal of Thoracic Disease, 5(S1): 36-46


Dabbs D.J., Schnitt S.J., Geyer F.C., Weigelt B., Baehner F.L., Decker T., Eusebi V., Fox S.B., Ichihara S., Lakhani S.R., Palacios J., Rakha E., Richardson A.L., Schmitt F.C., Tan P.H., Tse G.M., Vincent-Salomon A., Ellis I.O., Badve S., and Reis-Filho J.S., 2013, Lobular neoplasia of the breast revisited with emphasis on the role of e-cadherin immunohistochemistry, The American Journal of Surgical Pathology, 37(7): 1-11



Davies C., Pan H., Godwin J., G., Raina V., Abraham M., Alencar M.V.H., Badran A., Bonfill X., Bradbury J., Clarke M., Collins R., Davis S.R., Delmestri A., Forbes J.F., Haddad P., Houetal M.F., Inbar M., Khaled H., Kielanowska J., Kwan W.H., Mathew B.S., Mittra I., Müller B., Nicolucci A., Peralta O., Pernas F., Petruzelka L., Pienkowski T., Radhika R., Rajan B., Rubach M.T., Tort S., Urrútia G., Valentini M., and Peto R., 2013, Long-term effects of continuing adjuvant tamoxifen to 10 years versus stopping at 5 years after diagnosis of oestrogen receptor-positive breast cancer: ATLAS, a randomised trial, The Lancet, 381(9869): 805-816


Delpech Y., Coutant C., Hsu L., Barranger E., Iwamoto T., Barcenas C.H., Hortobagyi G.N., Rouzier R., Esteva F.J., and Pusztai L., 2013, Clinical benefit from neoadjuvant chemotherapy in oestrogen receptor-positive invasive ductal and lobular carcinomas, British Journal of Cancer, 108(2): 285-291

PMid:23299541 PMCid:PMC3566807


Engstrøm M.J., Opdahl S., Vatten L.J., Haugen O.A., and Bofin A.M., 2015, Invasive lobular breast cancer: the prognostic impact of histopathological grade, E-cadherin and molecular subtypes, Histopathology, 66(3): 409-419

PMid: 25283075 PMCid:PMC4329418


Li B.Y., and Li C.G., 2012, The pathological and clinical features of invasive lobular breast carcinoma and comprehensive treatment, China Medical Guide, 10(26): 59-60


Li X., Schwartz M.R., Ro J., Hamilton C.R., Ayala A.G., Truong L.D., and Zhai Q.J., 2014, Diagnostic utility of E-cadherin and P120 catenin cocktail immunostain in distinguishing DCIS from LCIS, International Journal of Clinical and Experimental Pathology, 7(5): 2551-2557


Menezes G.L., van den Bosch M.A., and Postma E.L., 2013, Invasive ductolobular carcinoma of the breast: spectrum of mammographic, ultrasound and magnetic resonance imaging findings correlated with proportion of the lobular component, Springer Plus, 2(1): 1-12

PMid:24340243 PMCid:PMC3858590


Nounou M.I., ElAmrawy F., Ahmed N., Abdelraouf K., Goda S., and Syed-Sha-Qhattal H., 2015, Conventional diagnosis and treatment modalities and recent patents and technologies, Breast Cancer(Auckl), 9(S2): 17-34

PMid:26462242 PMCid:PMC4589089


Oliveira T.M., Elias J.J., Melo A.F., Teixeira S.R., Filho S.C., Gonçalves L.M., Faria F.M., Tiezzi D.G., Andrade J.M., and Muglia V., 2014, Evolving concepts in breast lobular neoplasia and invasive lobular carcinoma, and their impact on imaging methods, Insights into Imaging, 5(2): 183-194

PMid:24633840 PMCid:PMC3999371


Park J.S., Choi D.H., Huh S.J., Park W., Kim Y., Nam S.J., Lee J.E., and Kil W.H., 2015, Comparison of clinicopathological features and treatment results between invasive lobular carcinoma and ductal carcinoma of the breast, Journal of Breast Cancer, 18(3): 285-290

PMid:26472980 PMCid:PMC4600694


Petridis C., Shinomiya I., Kohut K., Gorman P., Caneppele M., Shah V., Troy M., Pinder S.E., Hanby A., Tomlinson I., Trembath R.C., Roylance R., Simpson M.A., and Sawyer E.J., 2014, Germline CDH1 mutations in bilateral lobular carcinoma in suit, British Journal of Cancer, 110(4): 1053-1057

PMid:24366306 PMCid:PMC3929874


Rakha E.A., van Deurzen C.H., Paish E.C., Macmillan R.D., Ellis I.O., and Lee A.H., 2013, Pleomorphic lobular carcinoma of the breast: is it a prognostically significant pathological subtype independent of histological grade? Modern Pathology an Official Journal of the United States and Canadian Academy of Pathology Inc, 6(2): 496-501



Reed A.E.M., Kutasovic J.R., Lakhani S.R., and Simpson P.T., 2015, Invasive lobular carcinoma of the breast: morphology, biomarkers and 'omics, Breast Cancer Research, 17(1): 1-11

PMid:25849106 PMCid:PMC4310190


Sikora M.J., Cooper K.L., Bahreini A., Luthra S., Wang G.Y., Chandran U.R., Davidson N.E., Dabbs D.J., Welm A.L., and Oesterreich S., 2014, Invasive lobular carcinoma cell lines are characterized by unique estrogen-mediated gene expression patterns and altered tamoxifen response, Cancer Research, 74(5): 1463-1474

PMid:24425047 PMCid:PMC3955299


Sinn H.P., Helmchen B., Heil J., and Aulmann S., 2014, Lobular neoplasms and invasive lobular breast cancer, Der Pathologe, 35(1): 45-53



Sonnenblick A., Francis P.A., Azim H.A.J., de Azambuja E., Nordenskjöld B., Gutiérez J., Quinaux E., Mastropasqua M.G., Ameye L., Anderson M., Lluch A., Gnantl M., Goldhirsch A., Leo A.D., Barnadas A., Cortes-Funes H., Piccart M., and Crown J., 2015, Final 10-year results of the Breast International Group 2-98 phase III trial and the role of Ki67 in predicting benefit of adjuvant docetaxel in patients with oestrogen receptor positive breast cancer, European Journal of Cancer, 51(12): 1481-1489



Swain S.M., Im Y.H., Im S.A., Chan V., Miles D., Knott A., Clark E., Ross G., and Baselga J., 2014, Safety profile of pertuzumab with trastuzumab and docetaxel in patients from Asia with human epidermal growth factor receptor 2-positive metastatic breast cancer: results from the phase III trial CLEOPA-TRA, Oncologist, 19(7): 693-701

PMid:24869931 PMCid:PMC4077449

Cancer Genetics and Epigenetics
• Volume 5
View Options
. PDF(208KB)
. Online fPDF
Associated material
. Readers' comments
Other articles by authors
. Li W.Q.
. Zhai Z.W.
. Guo Z.F.
. Zhang D.W.
Related articles
. Invasive lobular carcinoma
. Immunohistochemistry and molecular biology
. Comprehensive treatmen
. Email to a friend
. Post a comment