The pathology of inherited breast cancer

doi:10.1080/00313020220147113

Pathology

Volume 34, Issue 4, 2002, Pages 309-314

https://doi.org/10.1080/00313020220147113 Get rights and content

Summary

Familial breast cancer has been recognised for many years. In the 1990s the genetic mechanism of inheritance of a proportion of these familial cancers was found to be attributable to germline mutation in either of two newly discovered genes, namely BRCA1 and BRCA2. Since the discovery of these genes, studies have been performed in which the pathological characteristics of familial cancers arising in patients with germline BRCA1 and BRCA2 mutation have been examined. A distinct pathological phenotype of high-grade, oestrogen receptor-negative breast cancer, often with medullary features, has been consistently described for BRCA1 cancers. A less distinct phenotype has been described for BRCA2 cancers. The discovery of genotype-phenotype correlation has significant implications for patient management and novel treatment strategies, not only for inherited cancers, but for breast cancer in general.

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2016, Surgery (United Kingdom)
Cellular pathology is a key component of the breast disease multidisciplinary team (MDT), representing the ‘gold standard’ in the diagnosis of breast cancer and providing crucial information for determination of prognosis and management. Material may be obtained for pathological examination using fine needle aspiration (FNA) cytology, needle core biopsy or surgical excision (histopathology). Common benign conditions include fibrocystic change, fibroadenomas, intraduct papillomas and radial scars. Carcinoma is by far the most common malignant tumour and may exist as in situ or invasive forms. The use of mammography in the NHS Breast Screening Programme (NHS BSP) has resulted in the detection of breast cancers at an earlier stage of development (e.g. in situ carcinoma and small, low-grade invasive carcinomas). A recent comprehensive independent review has acknowledged the risk of over-diagnosis, whilst supporting the continuation of the programme due to evidence of overall benefit in terms of a reduction in breast cancer mortality. A cellular pathology report for a malignant breast excision specimen should include comments on the factors most pertinent to prognosis and management, such as tumour type, size, grade, and presence of vascular invasion and lymph node metastases. Assessment of the proximity of the tumour to the surgical margins will inform decisions regarding further surgical excision and radiotherapy, while identification of lymph node metastases will prompt consideration for chemotherapy in suitable patients. Cellular pathology techniques can also be used in predicting the likelihood of tumour response to hormonal manipulation and newer treatments such as trastuzumab. The application of increasingly sophisticated genomic technologies to breast cancer has enhanced the classification of the disease whilst highlighting new levels of complexity, and may lead to an improvement in both prognostication as well as the ability to better identify patients who may particularly benefit from chemotherapy and novel molecularly targeted therapies.
Histologic features of melanoma associated with CDKN2A genotype
2015, Journal of the American Academy of Dermatology
Inherited susceptibility genes have been associated with histopathologic characteristics of tumors.
We sought to identify associations between histology of melanomas and CDKN2A genotype.
This was a case-control study design comparing 28 histopathologic tumor features among individuals with sporadic melanomas (N = 81) and cases from melanoma families with (N = 123) and without (N = 120) CDKN2A germline mutations.
Compared with CDKN2A⁻ cases, mutation carriers tended to have histologic features of superficial spreading melanoma subtype including higher pigmentation (P_trend = .02) and increased pagetoid scatter (P_trend = .07) after adjusting for age at diagnosis, sex, and American Joint Committee on Cancer thickness category. Similar associations were observed when comparing mutation carriers with a combined group of CDKN2A⁻ (wild type) and sporadic melanomas. The presence of spindle cell morphology in the vertical growth phase was also an important predictor of genotype. Of the 15 cases with this phenotype, none were observed to harbor a CDKN2A mutation.
Our study examined rare mutations and may have been underpowered to detect small, but biologically significant associations between histology and genotype.
Familial melanomas with CDKN2A mutations preferentially express a histologic phenotype of dense pigmentation, high pagetoid scatter, and a non-spindle cell morphology in the vertical growth phase.
Breast pathology
2013, Surgery (United Kingdom)
Cellular pathology is a key component of the breast disease multidisciplinary team, representing the ‘gold standard’ in the diagnosis of breast cancer and providing crucial information for determination of prognosis and management. Material may be obtained for pathological examination using fine needle aspiration (FNA) cytology, needle core biopsy or surgical excision (histopathology). Common benign conditions include fibrocystic change, fibroadenomas, intraduct papillomas and radial scars. Carcinoma is by far the most common malignant tumour and may exist as in situ or invasive forms. The use of mammography in the NHS Breast Screening Programme (NHS BSP) has resulted in the detection of breast cancers at an earlier stage of development (e.g. in situ carcinoma and small, low-grade invasive carcinomas) and a comprehensive independent review assessing the benefits and possible drawbacks of this approach is due to report during 2012. A cellular pathology report for a breast excision specimen should include comments on the factors most pertinent to prognosis and management, such as tumour type, size, grade, and presence of vascular invasion and lymph node metastases. Assessment of adequacy of excision will inform decisions regarding further surgical excision and radiotherapy while identification of lymph node metastases will prompt consideration for chemotherapy in suitable patients. Cellular pathology can also predict the likelihood of tumour response to hormonal manipulation and newer treatments such as trastuzumab. The application of increasingly sophisticated genomic technologies to breast cancer has enhanced the classification of the disease whilst highlighting new levels of complexity, and may lead to an improvement in both prognostication as well as the ability to better identify patients who may particularly benefit from chemotherapy and novel molecularly targeted therapies.
Unusual malignant tumors of the breast: MRI features and pathologic correlation
2010, European Journal of Radiology
Citation Excerpt :
Medullary carcinoma accounts for approximately 5% of all breast cancers [17]. It is mostly seen in young women and several studies have shown a higher incidence of this histotype in carriers of BRCA1 deleterious mutations [3,17]. Prognosis of medullary carcinoma is slightly better than that of IDC-NOS [17].
Unusual malignant breast tumors are well-differentiated subtypes of invasive ductal carcinoma, including mucinous, tubular, medullary and papillary carcinomas, and account for about 10% of malignant breast tumors. They are increasingly being encountered during magnetic resonance imaging (MRI) examinations of the breast. Therefore, breast radiologists should be aware of their appearance on MRI.
This review provides an overview of MRI characteristics of a range of unusual tumors (mucinous carcinoma, medullary carcinoma, tubular carcinoma, intraductal papillary carcinoma, intracystic papillary carcinoma and invasive papillary carcinoma), highlighting specific clues for diagnosis and correlating MRI and pathologic features. Many unusual breast tumors exhibit MRI features similar to those of benign or low suspicious lesions (oval shape, well-defined margins, high signal intensity on T2-weighted images, continuous increase kinetics, i.e. type I dynamic curve), leading to a possible misdiagnosis. Nevertheless, an understanding of pathologic features of these tumors, especially tissue content (mucinous, fibrous) and growth pattern, can help to define some specific clues for their diagnosis.
Breast pathology
2010, Surgery
Cellular pathology is a key component of the breast disease multidisciplinary team, representing the ‘gold standard’ in the diagnosis of breast cancer and providing information key to the determination of prognosis and management. Material may be obtained for pathological examination using fine needle aspiration (cytology) or core biopsy and surgical excision (histopathology). Common benign conditions include fibrocystic change, fibroadenomas, intraduct papillomas and radial scars. Carcinoma is by far the most common malignant tumour and may exist in in situ or invasive forms. The NHS Breast Screening Programme has resulted in the detection of less advanced breast cancers, for example in situ carcinoma and small, low-grade invasive carcinomas. A cellular pathology report for a breast excision specimen should include comments on the factors most pertinent to prognosis and management, such as tumour type, size, grade, and presence of vascular invasion and lymph node metastases. Assessment of adequacy of excision will inform decisions regarding further surgical excision and radiotherapy, while identification of lymph node metastases will prompt consideration for chemotherapy in suitable patients. Cellular pathology can also predict the likelihood of tumour response to hormonal manipulation and newer treatments such as trastuzumab.
Medullary cancer of the breast. Characterisation of a series of cases, 2010-2019
2020, Revista de Senologia y Patologia Mamaria
El carcinoma medular de la mama es un subtipo poco común de carcinoma invasivo que representa cerca de 3 al 5% de todos los casos de cáncer de mama. El objetivo fue caracterizar una serie de casos con diagnóstico anatomopatológico de carcinoma medular de la mama, del Hospital Clínico Quirúrgico Docente Joaquín Albarrán, en el periodo 2010 al 2019.
Se realizó un estudio retrospectivo, descriptivo y observacional, en el cual se revisaron los registros de biopsias recolectándose variables como, edad y características macroscópicas e histológicas.
En el periodo de 2010 a 2019 se realizó el diagnóstico histopatológicamente de 9 casos de carcinoma medular de la mama, de los cuales el 77,8% fueron carcinoma medular de la mama típico y 22,2%, atípico. Solo un 33,3% de las lesiones presentaban necrosis intratumoral; la permeación linfática estaba presente en el 100% de los casos; la metástasis ganglionar se confirmó en el 33,3% de los casos. El estudio por inmunohistoquímica, reveló que el 88,9% de los tumores no expresaron receptores hormonales y Her-2, por lo cual fueron clasificados como subtipo molecular triple negativo o basal.
Para el diagnóstico histopatológico de CMM es fundamental la presencia de infiltrado linfoplasmocítico, considerando siempre la intensidad y el patrón de distribución de los linfocitos y células plasmáticas en relación con las características de las células tumorales (disposición y características individuales). El subtipo molecular triple negativo fue la más frecuente.
Medullary carcinoma of the breast is a rare subtype of invasive carcinoma that accounts for about 3-5% of all cases of breast cancer. The aim of this study was to characterize a series of cases with anatomopathological diagnosis of medullary carcinoma of the mother, from Hospital Clínico Quirúrgico Docente Joaquín Albarrán, in the period 2010 to 2019.
A retrospective, descriptive and observational study was conducted, in which the biopsy records were reviewed, collecting variables such as age and macroscopic and histological characteristics.
In the period from 2010 to 2019, the histopathological diagnosis of 9 cases of medullary carcinoma of the breast was made, of which 77.8% were typical medullary carcinoma of the breast and 22.2%, atypical. Only 33.3% of the lesions presented intratumoral necrosis; lymphatic permeation was present in 100% of cases; lymph node metastasis was confirmed in 33.3% of cases; The immunohistochemical study revealed that 88.9% of the tumors did not express hormonal and Her-2 receptors, so they were classified as triple negative or basal molecular subtype.
For the histopathological diagnosis of CMM, the presence of lymphoplasmocytic infiltrate is essential, always detecting the intensity and distribution pattern of lymphocytes and plasma cells in relation to the characteristics of tumor cells (individual disposition and characteristics). The triple negative molecular subtype was the most frequent.

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The pathology of inherited breast cancer

Summary

Trends Genet

Am J Hum Genet

Eur J Cancer

Population-based estimate of the average age-specific cumulative risk of breast cancer for a defined set of protein-truncating mutations in BRCA1 and BRCA2. Australian Breast Cancer Family Study

Cancer Epidemiol Biomarkers Prev

BRCA1 mediates ligand-independent transcriptional repression of the estrogen receptor

Proc Natl Acad Sci USA

Estimates of the gene frequency of BRCA1 and its contribution to breast and ovarian cancer incidence

Am J Hum Genet

Genetic linkage analysis in familial breast and ovarian cancer: results from 214 families. The Breast Cancer Linkage Consortium

Am J Hum Genet

Breast cancer in Australian women under the age of 40

Cancer Causes Control

Why are the majority of hereditary cases of early-onset breast cancer sporadic? A simulation study

Cancer Epidemiol Biomarkers Prev

Mutations and polymorphisms in the familial early-onset breast cancer (BRCA1) gene. Breast Cancer Information Core

Hum Mutat

Epidemiology of breast carcinoma III: relationship of family history to tumor type

Cancer

Tubular carcinoma of the breast: association with multicentricity, bilaterality, and family history of mammary carcinoma

Am J Clin Pathol

Pathology and heredity of breast cancer in younger women

J Natl Cancer Inst Monogr

BRCA-associated breast cancer in young women

J Clin Oncol

Multifactorial analysis of differences between sporadic breast cancers and cancers involving BRCA1 and BRCA2 mutations

J Natl Cancer Inst

Influence of BRCA1 mutations on nuclear grade and estrogen receptor status of breast carcinoma in Ashkenazi Jewish women

Cancer

BRCA2 hereditary breast cancer pathophenotype

Breast Cancer Res Treat

Germ line mutation at BRCA1 affects the histoprognostic grade in hereditary breast cancer

Cancer Res