Abstract
An accurate pathological assessment of core biopsies or resection specimens provides important information on the major features of breast cancer, such as tumor type, size, biological characteristics, lymph node status, stage, and extent of residual disease in case of neoadjuvant chemotherapy, and is crucial for ensuring an appropriate patient management. In the era of molecular medicine and tailored therapies, the pathologic assessment of primary tumor still represents an essential guide for oncologists and surgeons to inform the choice of the best treatment options available for individual patients. Therefore, the management of patients with breast cancer detected through imaging or symptomatic presentation depends heavily on the quality of the pathology service.
Access this chapter
Tax calculation will be finalised at checkout
Purchases are for personal use only
References
Wolff AC, Hammond ME, Schwartz JN et al (2007) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for human epidermal growth factor receptor 2 testing in breast cancer. J Clin Oncol 25:118–145
Hammond ME, Hayes DF, Wolff AC et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Oncol Pract 6:195–197
Bossuyt V, Provenzano E, Symmans WF et al (2015) Recommendations for standardized pathological characterization of residual disease for neoadjuvant clinical trials of breast cancer by the BIG-NABCG collaboration. Ann Oncol 26(7):1280–1291
Provenzano E, Bossuyt V, Viale G et al (2015) Standardization of pathologic evaluation and reporting of postneoadjuvant specimens in clinical trials of breast cancer: recommendations from an international working group. Mod Pathol 28(9):1185–1201
Lakhani S, Ellis I, Schnitt S et al (2012) WHO classification of tumours of the breast, 4. Aufl edn. IARC Press, Lyon
Colleoni M, Rotmensz N, Maisonneuve P et al (2012) Outcome of special types of breast cancer. Ann Oncol 23(6):1428–1436
Arpino G, Clark GM, Mohsin S et al (2000) Adenoid cystic carcinoma of the breast: molecular markers, treatment, and clinical outcome. Cancer 94:2119–2127
Leibl S, Gogg-Kammerer M, Sommersacher A et al (2005) Metaplastic breast carcinomas: are they of myoepithelial differentiation? Immunohistochemical profile of the sarcomatoid subtype using novel myoepithelial markers. Am J Surg Pathol 29:347–353
Pestalozzi BC, Zahrieh D, Mallon E et al (2008) Distinct clinical and prognostic features of infiltrating lobular carcinoma of the breast: combined results of 15 international breast cancer study group clinical trials. J Clin Oncol 26:3006–3014
Viale G, Rotmensz MP et al (2009) Lack of prognostic significance of “classic” lobular breast carcinoma: a matched, single institution series. Breast Cancer Res Treat 117:211–214
Edge SB, Byrd DR, Compton CC et al (2010) AJCC cancer staging manual, 7th edn. Springer, New York
Ellis IO, Carder P, Hales S et al (2016) Pathology reporting of breast disease in surgical excision specimens incorporating the dataset for histological reporting of breast cancer. Published by The Royal College of Pathologists, 73
Henson DE, Ries L, Freedman LS et al (1991) Relationship among outcome, stage of disease, and histologic grade for 22,616 cases of breast cancer. The basis of a prognostic index. Cancer 68:2142–2149
Page DL, Ellis IO, Elston CW (1995) Histologic grading of breast cancer let’s do it. Am J Clin Pathol 103:123–124
Rakha EA, El-Sayed ME, Lee AH et al (2008) Prognostic significance of Nottingham histologic grade in invasive breast carcinoma. J Clin Oncol 26:3153–3158
Patey DH, Scarff RW (1928) The position of histology in the prognosis of carcinoma of the breast. Lancet 1:801–804
Bloom HJ, Richardson WW (1957) Histological grading and prognosis in breast cancer. Br J Cancer 11:359–377
Elston CW, Ellis IO (1991) Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: experience from a large study with long-term follow-up. Histopathology 19(5):403–401
Dunne B, Going JJ (2001) Scoring nuclear pleomorphism in breast cancer. Histopathology 39:259–265
Verhoeven D, Bourgeois N, Derde MP et al (1990) Comparison of cell growth in different parts of breast cancers. Histopathology 17:505–509
Connor AJM, Pinder SE, Elston CW et al (1997) Intratumoural heterogeneity of proliferation in invasive breast carcinoma evaluated with MIB1 antibody. Breast 6:171–176
Harris GC, Denley HE, Pinder SE, Lee AH, Ellis IO, Elston CW et al (2003) Correlation of histologic prognostic factors in core biopsies and therapeutic excisions of invasive breast carcinoma. Am J Surg Pathol 27:11–15
O’Shea AM, Rakha EA, Hodi Z et al (2011) Histological grade of invasive carcinoma of the breast assessed on needle core biopsy—modifications to mitotic count assessment to improve agreement with surgical specimens. Histopathology 59:543–548
Pinder SE, Ellis IO, Galea M et al (1994) Pathological prognostic factors in breast cancer. III. Vascular invasion: relationship with recurrence and survival in a large study with long-term follow-up. Histopathology 24:41–47
Lee AH, Pinder SE, Macmillan RD et al (2006) Prognostic value of lymphovascular invasion in women with lymph node negative invasive breast carcinoma. Eur J Cancer 42:357–362
Mohammed RA, Ellis IO, Lee AH, Martin SG (2009) Vascular invasion in breast cancer; an overview of recent prognostic developments and molecular pathophysiological mechanisms. Histopathology 55:1–9
Braun M, Flucke U, Debald M et al (2008) Detection of lymphovascular invasion in early breast cancer by D2-40 (podoplanin): a clinically useful predictor for axillary lymph node metastases. Breast Cancer Res Treat 112:503–511
Fisher B, Anderson S, Bryant J et al (2002) Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 347:1233–1241
Arriagada R, Lê MG, Rochard F, Contesso G (1996) Conservative treatment versus mastectomy in early breast cancer: patterns of failure with 15 years of follow-up data. Institut Gustave-Roussy breast cancer group. J Clin Oncol 14:1558–1564
Blichert-Toft M, Rose C, Andersen JA et al (1992) Danish randomized trial comparing breast conservation therapy with mastectomy: six years of life-table analysis. Danish breast cancer cooperative group. J Natl Cancer Inst Monogr 11:19–25
Poggi MM, Danforth DN, Sciuto LC et al (2003) Eighteen-year results in the treatment of early breast carcinoma with mastectomy versus breast conservation therapy: the National Cancer Institute Randomized trial. Cancer 98:697–702
Van Dongen JA, Voogd AC, Fentiman IS et al (2000) Long-term results of a randomized trial comparing breast-conserving therapy with mastectomy: European Organization for Research and Treatment of Cancer 10801 trial. J Natl Cancer Inst 92:1143–1150
Veronesi U, Cascinelli N, Mariani L et al (2002) Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 347:1227–1232
Halyard MY, Wasif N, Harris EE et al (2012) ACR appropriateness criteria local-regional recurrence (LR) and salvage surgery: breast cancer. Am J Clin Oncol 35:178–182
Park CC, Mitsumori M, Nixon A et al (2000) Outcome at 8 years after breast conserving surgery and radiation therapy for invasive breast cancer: influence of margin status and systemic therapy on local recurrence. J Clin Oncol 18:1668–1675
Leong C, Boyages J, Jayasinghe UW et al (2004) Effect of margins on ipsilateral breast tumor recurrence after breast conservation therapy for lymph node negative breast carcinoma. Cancer 100:1823–1832
Dooley WC, Parker J (2005) Understanding the mechanisms creating false positive lumpectomy margins. Am J Surg 190:606–608
Esbona K, Li Z, Wilke LG (2012) Intraoperative imprint cytology and frozen section pathology for margin assessment in breast conservation surgery: a systematic review. Ann Surg Oncol 19:3236–3245
Osborn JB, Keeney GL, Jakub JW et al (2011) Cost-effectiveness analysis of routine frozen-section analysis of breast margins compared with reoperation for positive margins. Ann Surg Oncol 18:3204–3209
De Mascarel I, MacGrogan G, Debled M et al (2008) Distinction between isolated tumor cells and micrometastases in breast cancer: is it reliable and useful? Cancer 112:1672–1678
Cserni G, Bianchi S, Vezzosi V et al (2008) Variations in sentinel node isolated tumour cells/micrometastasis and non-sentinel node involvement rates according to different interpretations of the TNM definitions. Eur J Cancer 44:2185–2191
Veronesi U, Paganelli G, Galimberti V et al (1997) Sentinel-node biopsy to avoid axillary dissection in breast cancer with clinically negative lymph-nodes. Lancet 349(9069):1864–1867
Viale G, Bosari S, Mazzarol G et al (1999) Intraoperative examination of axillary lymph nodes in breast carcinoma patients. Cancer 85(11):2433–2438
Turner RR, Olilla DW, Krasne DL, Giuliano AE (1997) Histopathologic validation of sentinel lymph node hypothesis for breast carcinoma. Ann Surg 226(3):271–276
Taniyama K, Motoshita J, Sakane J et al (2006) Combination analysis of a whole lymph node by one-step nucleic acid amplification and histology for intraoperative detection of micrometastasis. Pathobiology 73(4):183–191
Tsujimoto M, Nakabayashi K, Yoshidome K et al (2007) One-step nucleic acid amplification for intraoperative detection of lymph node metastasis in breast cancer patients. Clin Cancer Res 13(16):4807–4816
Tamaki Y, Akiyama F, Iwase T et al (2009) Molecular detection of lymph node metastases in breast cancer patients: results of a multicenter trial using the one-step nucleic acid amplification assay. Clin Cancer Res 15(8):2879–2884
Hansen NM, Grube B, Ye X et al (2009) Impact of micrometastasis in the sentinel node of patients with invasive breast cancer. J Clin Oncol 27(28):4679–4684
Giuliano AE, Hunt KK, Ballman KV et al (2011) Axillary dissection vs no axillary dissection in women with invasive breast cancer and sentinel node metastasis: a randomized clinical trial. JAMA 305:569–575
Giuliano AE, McCall L, Beitsch P et al (2010) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: the American College of Surgeons oncology group Z0011 randomized trial. Ann Surg 252:426–432
Giuliano AE, Ballman K, McCall L et al (2016) Locoregional recurrence after sentinel lymph node dissection with or without axillary dissection in patients with sentinel lymph node metastases: long-term follow-up from the american college of surgeons oncology group (alliance) ACOSOG Z0011 randomized trial. Ann Surg 264(3):413–420
Coates AS, Winer EP, Goldhirsch A et al (2015) Tailoring therapies-improving the management of early breast cancer: St. Gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol 26:1533–1546
Rakha EA, Reis-Filho JS, Ellis IO (2010) Combinatorial biomarker expression in breast cancer. Breast Cancer Res Treat 120(2):293–308
Perou CM, Sorlie T, Eisen MB et al (2000) Molecular portraits of human breast tumours. Nature 406(6797):747–752
Anderson WF, Chatterjee N, Ershler WB, Brawley OW (2002) Estrogen receptor breast cancer phenotypes in the surveillance, epidemiology, and end results database. Breast Cancer Res Treat 76:27–36
Dunnwald LK, Rossing MA, Li CI (2007) Hormone receptor status, tumor characteristics, and prognosis: a prospective cohort of breast cancer patients. Breast Cancer Res 9:R6
Putti TC, El-Rehim DMA, Rakha EA et al (2005) Estrogen receptor-negative breast carcinomas: a review of morphology and immunophenotypical analysis. Mod Pathol 18:26–35
Group EBCTC (2005) Effects of chemotherapy and hormonal therapy for early breast cancer on recurrence and 15-year survival: an overview of the randomised trials. Lancet 365:1687–1717
Badve S, Nakshatri H (2009) Oestrogen-receptor-positive breast cancer: towards bridging histopathological and molecular classifications. J Clin Pathol 62:6–12
Oh DS, Troester MA, Usary J et al (2006) Estrogen-regulated genes predict survival in hormone receptor-positive breast cancers. J Clin Oncol Off J Am Soc Clin Oncol 24:1656–1664
Group EBCTC (1998) Tamoxifen for early breast cancer: an overview of the randomised trials. Lancet 351:1451–1467
Goldhirsch A, Ingle JN, Gelber RD et al (2009) Thresholds for therapies: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol 20:1319–1329
Hammond ME, Hayes DF, Dowsett M et al (2010) American Society of Clinical Oncology/College of American Pathologists guideline recommendations for immunohistochemical testing of estrogen and progesterone receptors in breast cancer. J Clin Oncol 28:2784–2789
Kohler BA, Sherman RL, Howlader N et al (2015) Annual report to the nation on the status of cancer, 1975–2011, featuring incidence of breast cancer subtypes by race/ethnicity, poverty, and state. J Natl Cancer Inst 30:107
Bose R, Kavuri SM, Searleman AC et al (2013) Activating HER2 mutations in HER2 gene amplification negative breast cancer. Cancer Discov 3(2):224–237
Greulich H, Kaplan B, Mertins P et al (2012) Functional analysis of receptor tyrosine kinase mutations in lung cancer identifies oncogenic extracellular domain mutations of ERBB2. Proc Natl Acad Sci U S A 109(36):14476–14481
Wagle N, Lin NU, Richardson AL et al (2014) Whole exome sequencing of HER2+ metastatic breast cancer from patients with or without prior trastuzumab: a correlative analysis of TBCRC003. Presented at the San Antonio Breast Cancer Symposium
Ross JS, Slodkowska EA, Symmans WF et al (2009) The HER-2 receptor and breast cancer: ten years of targeted anti-HER-2 therapy and personalized medicine. Oncologist 14:320–368
Moasser MM, Krop IE (2015) The evolving landscape of HER2 targeting in breast cancer. JAMA Onocol 1(8):1154–1161
Salmon DJ, Leyland-Jones B, Shak S et al (2001) Use of chemotherapy plus a monoclonal antibody against HER2 for metastatic breast cancer that overexpresses HER2. N Engl J Med 344(11):783–792
Piccart-Gebhart MJ, Procter M, Leyland-Jones B et al (2005) Trastuzumab after adjuvant chemotherapy in HER2-positive breast cancer. N Engl J Med 353:1659–1672
Goldhirsch A, Gelber RD, Piccart-Gebhart MJ et al (2013) 2 years versus 1 year of adjuvant trastuzumab for HER2-positive breast cancer (HERA): an open-label, randomized controlled trial. Lancet 382:1021–1028
Perez EA, Romond EH, Suman VJ et al (2011) Four-year follow-up of trastuzumab plus adjuvant chemotherapy for operable human epidermal growth factor receptor 2-positive breast cancer: joint analysis of data from NCCTG N9831 and NSABP B-31. J Clin Oncol 29:3366–3373
Perez EA, Romond EH, Suman VJ et al (2014) Trastuzumab plus adjuvant chemo-therapy for human epidermal growth factor receptor 2-positive breast cancer: planned joint analysis of overall survival from NSABP B-31 and NCCTG N9831. J Clin Oncol 32:3744–3752
Guarneri V, Frassoldati A, Bottini A et al (2012) Preoperative chemotherapy plus trastuzumab, lapatinib, or both in human epidermal growth factor receptor 2-positive operable breast cancer: results of the randomized phase II CHER-LOB study. J Clin Oncol 30(16):1989–1995
Baselga J, Cortes J, Kim SB et al (2012) Pertuzumab plus trastuzumab plus docetaxel for metastatic breast cancer. N Engl J Med 366(2):109–119
Swain SM, Baselga J, Kim SB et al (2015) Pertuzumab, trastuzumab, and docetaxel in HER2-positive metastatic breast cancer. N Engl J Med 372(8):724–734
Baselga J, Bradbury I, Eidtmann H et al (2012) Lapatinib with trastuzumab for HER2-positive early breast cancer (NeoALTTO): a randomised, open-label, multicentre, phase 3 trial. Lancet 379:633–640
Gianni L, Bienkowski T, Im YH et al (2012) Efficacy and safety of neoadjuvant pertuzumab and trastuzumab in women with locally advanced, inflammatory, or early HER2-positive breast cancer (NeoSphere): a randomised multicentre, open-label, phase 2 trial. Lancet Oncol 13(1):25–32
IBCSG Trial 39–11/BIG 4–11 (APHINITY)
Press MF, Sauter G, Bernstein L et al (2005) Diagnostic evaluation of HER-2 as a molecular target: an assessment of accuracy and reproducibility of laboratory testing in large, prospective, randomized clinical trials. Clin Cancer Res 11(18):6598–6607
Perez EA, Suman VJ, Davidson NE et al (2006) HER2 testing by local, central, and reference laboratories in specimens from the North Central Cancer Treatment Group N9831 intergroup adjuvant trial. J Clin Oncol 24(19):3032–3038
Viale G, Slaets L, Bogaerts J et al (2014) High concordance of protein (by IHC), gene (by FISH; HER2 only), and microarray readout (by TargetPrint) of ER, PgR, and HER2: results from the EORTC 10041/BIG 03-04 MINDACT trial. Ann Oncol 25:816–823
Thor AD, Liu S, Moore DH, Edgerton SM (1999) Comparison of mitotic index, in vitro bromodeoxyuridine labeling, and MIB-1 assays to quantitate proliferation in breast cancer. J Clin Oncol 17:470–477
De Azambuja E, Cardoso F, de Castro G et al (2007) Ki-67 as prognostic marker in early breast cancer: a meta-analysis of published studies involving 12 155 patients. Br J Cancer 96:1504–1513
Jonat W, Arnold N (2011) Is the Ki-67 labelling index ready for clinical use? Ann Oncol 22:500–502
Sorlie T, Perou CM, Tibshirani R et al (2001) Gene expression patterns of breast carcinomas distinguish tumor subclasses with clinical implications. Proc Natl Acad Sci U S A 98(19):10869–10874
Parker JS, Mullins M, Cheang MC et al (2009) Supervised risk predictor of breast cancer based on intrinsic subtypes. J Clin Oncol 27(8):1160–1167
Prat A, Pineda E, Adamo B et al (2015) Clinical implications of the intrinsic molecular subtypes of breast cancer. Breast Suppl 2:S26–S35
Van’t Veer LJ, Dai H, van de Vijver MJ et al (2002) Gene expression profiling predicts clinical outcome of breast cancer. Nature 415(6871):530–536
Wittner BS, Sgroi DC, Ryan PD et al (2008) Analysis of the MammaPrint breast cancer assay in a predominantly postmenopausal cohort. Clin Cancer Res 14(10):2988–2993
Paik S, Shak S, Tang G et al (2004) A multigene assay to predict recurrence of tamoxifen-treated, node-negative breast cancer. N Engl J Med 351(27):2817–2826
Dowsett M, Nielsen TO, A’Hern R et al (2011) Assessment of Ki67 in breast cancer: recommendations from the International Ki67 in Breast Cancer working group. J Natl Cancer Inst 103:1656–1664
Cheang MCU, Chia SK, Voduc D, Gao D, Leung S, Snider J et al (2009) Ki67 index, HER2 status, and prognosis of patients with Luminal B breast cancer. J Natl Cancer Inst 101:736–750
Goldhirsch A, Winer EP, Coates AS, Gelber RD, Piccart-Gebhart M, Thürlimann B et al (2013) Personalizing the treatment of women with early breast cancer: highlights of the St. Gallen international expert consensus on the primary therapy of early breast cancer. Ann Oncol 24:2206–2223
Prat A, Cheang MC, Martín M, Parker JS, Carrasco E, Caballero R et al (2013) Prognostic significance of progesterone receptor e positive tumor cells within immunohistochemically defined Luminal A breast cancer. J Clin Oncol 31:203–209
Maisonneuve P, Disalvatore D, Rotmensz N, Curigliano G, Colleoni M, Dellapasqua S et al (2014) Proposed new clinicopathological surrogate definitions of Luminal A and Luminal B (HER2-negative) intrinsic breast cancer subtypes. Breast Cancer Res 16:R65
Author information
Authors and Affiliations
Corresponding author
Editor information
Editors and Affiliations
Rights and permissions
Copyright information
© 2017 Springer International Publishing AG
About this chapter
Cite this chapter
Vingiani, A., Viale, G. (2017). The Pathology Report. In: Veronesi, U., Goldhirsch, A., Veronesi, P., Gentilini, O., Leonardi, M. (eds) Breast Cancer. Springer, Cham. https://doi.org/10.1007/978-3-319-48848-6_16
Download citation
DOI: https://doi.org/10.1007/978-3-319-48848-6_16
Published:
Publisher Name: Springer, Cham
Print ISBN: 978-3-319-48846-2
Online ISBN: 978-3-319-48848-6
eBook Packages: MedicineMedicine (R0)