British Mtdual Bullttm (1991) Vol 47, No. 2, pp. 251-257 © The British Council 1991
Classification of benign breast disorders The AND I classification based on physiological processes within the normal breast L E Hughes Department of Surgery, University of Wales College of Medicine, Cardiff, UK
Terminology in benign breast conditions has been confused by multiplicity of terms which do not relate accurately to clinical or histological patterns. Further confusion arises because terminology is not based on sound concepts of pathogenesis. The ANDI classification has been put forward as a nomenclature based on pathogenesis to replace the division of benign breast disorders into 'normal' and 'disease'. It recognizes that a spectrum exists for most conditions which extends from normal, through mild abnormality—'aberrations'—to disease. This classification allows precise definition of an individual patient problem in terms of pathogenesis, histology and clinical implications. It has proved helpful in deciding rational clinical management and in teaching the significance of benign breast disorders.
Attitudes to benign breast conditions have changed radically in recent years. Classically they have been considered only in relation to die need to exclude malignancy, other aspects have often been regarded as psychosomatic. Now the more severe manifestations are accepted as a significant cause of morbidity, yet less severe symptoms are so common that they must be regarded as lying within the range of normality. It is this fact that benign conditions may both lie within the range of normality or reflect severe disease which has caused great conceptual problems. Nomenclature has not kept up with the pace of change. Fibro-
252
BREAST DISEASE
cystic disease (histological terminology) continues as the term used for the clinical syndrome of premenstrual pain and nodularity. It was unfortunate that early workers noted many histological patterns in biopsies of breast nodules including fibrosis, cyst formation, epithelial hyperplasia and lymphocytic infiltration and assumed a causative relationship. As different workers placed differing emphases on minor aspects of these pathological changes, a wide variety of terms grew up. Early terms tended to reflect clinical concepts (e.g. chronic mastitis) but later they reflected histological appearances with terms such as hyperplastic cystic disease, fibroadenosis, fibrocystic disease etc. Since the term hyperplasia tends to be linked in the minds of clinicians with cancer, the use of this term often leads to an unwarranted association between 'fibrocystic disease' and cancer. The changed attitudes of recent years have arisen from in depth studies which have defined clinical syndromes more precisely, and endocrine studies which have provided a physiological basis for painful nodularity. RECOGNITION OF THE NORMALITY OF MUCH BENIGN BREAST 'DISEASE' In the 1960s a number of seminal studies demonstrated that the changes commonly described as fibroadenosis were widely distributed in patients who had not claimed to be symptomatic or demonstrated overt disease. There were two outstanding British examples. Parks1 showed, from studies of both surgical and autopsy specimens, a complete gradation between normal histology and disease; for example between developing lobules and fibroadenomas and between involuting lobules and macroscopic cysts. He also showed that epithelial hyperplasia is so common around the menopause as to be regarded as normal and that these lesions—so often regarded as indicative of cancer risk—could regress without treatment. In the second, Sandison2 showed from an extensive autopsy study that most of the changes previously regarded as disease are so common that they must be regarded as lying within the spectrum of normality. Other workers have confirmed these findings, and recently the concept has been taken further by proposing fibrocystic disease to be a 'non-disease'.3 While this concept may be of value in dispelling the supposed association between benign conditions and cancer, to regard it as a non entity is of little help
ANDI NOMENCLATURE
253
in the clinical management of those patients who have severe symptoms. Studies in Cardiff over the past 20 years have shown the high incidence of painful nodularity—approximately 50% of patients presenting to a breast clinic and two thirds of a population of working women report mastalgia. The clinical significance of mastalgia was quantified in the Cardiff Mastalgia Clinic where a classification was proposed,4 and the impact on patients lives assessed by means of breast pain charts and visual linear analogue scales. While most patients with breast pain were concerned with cancer and can be managed by adequate reassurance, mastalgia was found to be sufficiently severe in a minority to act as a major interference with quality of life and to be regarded as 'disease'. In its severe forms, it is associated with demonstrable endocrine abnormalities5 but not with specific histological patterns. It responds to appropriate therapy in a non-placebo fashion.6 NEED FOR A NEW NOMENCLATURE Thus is was becoming clear that any nomenclature should describe symptomatology, histological patterns and endocrine processes accurately and meaningfully in terms of pathogenesis, and be able to cover a spectrum from normality to severe disease. Review of earlier nomenclature showed that existing problems related to four main areas—the wide variety of terms in use, (more than 40 synonyms have been used for painful nodularity), the border-line between normal and abnormal, correlation of clinical symptoms and signs with histological changes and the assessment of premalignant potential. The border-line between normal and abnormal needs to be denned in terms of symptomatology as well as histology. Cyclical menstrual changes superimposed on the broader changes of breast development, pregnancy and involution lead to a wide spectrum of breast symptoms and of histological patterns. It is obviously important to try to define the point at which the limits of normality merge into abnormality. This is best done in terms of incidence and clinical impact. If present in a large majority of women both symptoms and histological patterns must be regarded as normal. Clinical impact is assessed in terms of quality of life or malignant potential. As mechanisms of pathogenesis become better understood, it may be possible to improve on our present attempts to define abnormal physiological parameters.
254
BREAST DISEASE
Unwarranted correlation of clinical with histological patterns has arisen because a causal relationship has been assumed with histology when a clinical area of nodularity has been biopsied. While the pathology of a fibroadenoma or cyst clearly correlates with the clinical finding, the same is not true for nodularity, which has no constant underlying histological abnormality. The use of the term hyperplasia has frequently led to an implication of premalignancy. Only since the high incidence of hyperplastic changes in normal breast tissue has been recognized has it been realized that hyperplasias must be denned much more precisely before they can be correlated with cancer risk, as elegantly shown by Page and his co-workers.7 It was against this background that the need was felt to develop a new nomenclature that would give a comprehensive framework into which individual conditions could be placed in a meaningful way in relation to clinical significance and management. Since most benign breast conditions arise on a background of the normal changes seen in relation to breast development, cyclical changes, pregnancy and involution, the normal processes within these periods of reproductive life have been used as the basis on which the nomenclature has been built. THE AND I CONCEPT These considerations lay behind the development of the AND I concept (Aberrations of Normal Development and Involution). This was first put forward to a national breast conference in Cardiff in 1982, and later published.8 A British working party was set up consisting of Surgeons, Radiologists and Pathologists, together with European and American representatives, and produced a final version (Table 1) which is awaiting formal publication. An example of the reasoning leading to this concept can be found in fibroadenoma—conventionally considered to be a benign tumour. Parks' work1 showed a full spectrum between normal lobules, large lobules which cannot be differentiated histologically from fibroadenomas, and clinical fibroadenomas. Hence subclinical fibroadenomas are much commoner than clinical ones. Fibroadenomas show features different to most benign tumours. Growth is not progressive, most fibroadenomas reach a size of 1-2 cm and then remain static. If pregnancy supervenes they lactate, showing greater hormone dependence than typical benign tumours. Finally, those that persist to the menopause regress leav-
Table 1 Aberrations of normal development and involution Aberration Stage (peak age in yrs)
Normal process
Early reproductive period (15-25)
Disease state Clinical presentation
Lobule formation
Fibroadenoma
Discrete lump
Stroma formation
Juvenile hypertrophy
Excessive breast development
Mature reproductive period (25-40)
Cyclical hormonal effects on glandular tissue and stroma
Exaggerated cyclical effects
Cyclical mastalgia and nodularity generalised or discrete
Involution (35-55)
Lobular involution (including microcysts, apocrine change fibrosis, adenosis)
Macrocysts
Discrete lumps
Sclerosing lesions
X-ray abnormalities
Ductal involution (including periductal round cell infiltrates)
Duct dilatation
Nipple discharge
Periductal fibrosis
Nipple retraction
Mild epithelial hyperplasia
Histological report
Epithelial turnover
Giant fibroadenoma Multiple fibroadenomas
Periductal mastitis with bacterial infection and abscess formation
ANDI N OMENCLA
Underlying condition
Epithelial hyperplasia with atypia to
256
BREAST DISEASE
ing a fibrous mass which may calcify. All these attributes are better considered as an aberration of normal lobular development than a pathological tumour. The spectrum of fibroadenoma extends from enlarged lobules (found histologically in most breasts), through to an aberration of normal lobular development (the clinical fibroadenoma), to disease, i.e. multiple or giant fibroadenomas. Two or 3 fibroadenomas are quite common—sufficient to still be regarded as an aberration—but 5 or more lesions are uncommon—so uncommon that they can be regarded as disease both from the point of view of rarity, the concern they cause the patient and the difficulty of management when a number of discrete fibroadenomas involve each breast. Similarly with size, although most fibroadenomas are only 1 cm or so in diameter, 2 or even 3 cm lesions are sufficiently common to be regarded as an aberration. But lesions of 5 cm or more are quite rare, and also behave differently. These giantfibroadenomasusually show continuing growth, and so become a management problem. They can best be regarded as disease, again both from the point of view of rarity and the problems they cause the patient. So, now it is possible to look at AND I (Table 1) as a two dimensional classification. The vertical dimension reflects the reproductive periods—breast development, cyclical change and involution—while the horizontal element covers the spectrum from normality through aberration to disease. Also included in the horizontal element, the clinical presentation is given its own column to emphasize that histological and clinical aspects correlate for some conditions, in others they do not. By using this two dimensional approach most of the common benign conditions of the breast can be fitted into this framework. A full explanation and description of the concept is given elsewhere.9 Its value must be judged in relation to its usefulness in conveying concepts of pathogenesis, and in management by encouraging the definition of the point along the spectrum where a clinical presentation lies. IMPLICATION FOR THE MANAGEMENT OF BENIGN BREAST DISORDERS This concept implies that most benign breast disorders can be regarded as no more than aberrations of normal processes and hence do not call for active specific treatment. Increasingly this is becoming accepted—as an example is the trend towards conservative management of fibroadenoma—a concept which follows auto-
ANDI NOMENCLATURE
257
matically from the ANDI classification. Management now becomes based on considerations such as accurate diagnosis, patient concern and interference with quality of life, rather than on the need to treat a disease. REFERENCES 1 Parks AG. The microanatomy of the breast. Ann R Coll Surg Engl 1959; 25: 235-251 2 Sandison AT. An Autopsy Study of the Human Breast. Natl Cancer Inst Monogr 8. Washington: US Department of Health Education and Welfare, 1962 3 Love SM, Gelman RS, Silcn W. Fibrocystic 'disease' of the breast—a nondisease. N Engl J Med 1982; 307: 1010-1014 4 Preece PE, Hughes LE, Mansel RE, Baum M, Bolton P, Gravelle IH. Clinical Syndromes of Mastalgia. Lancet 1976; ii: 670-673 5 Kumar S, Mansel RE, Hughes LE, Edwards CA, Scanlon MF. Production of response to endocrine therapy in pronounced cyclical mastalgia using dynamic tests of prolactin release. Clin Endocrinol 1985; 23: 699-704 6 Pye JK, Mansel RE, Hughes LE. Clinical experience of Drug Treatments for Mastalgia. Lancet 1985; ii: 373-7 7 Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative disease. N Engl J Med 1985; 312: 146-151 8 Hughes LE, Mansel RE, Webster DJT. Aberrations of normal development and involution (ANDI). A new perspective on pathogencsis and nomenclature of benign breast disorders. Lancet 1987; (?): 1316-19 9 Hughes LE, Mansel RE, Webster DJT. Benign disorders and diseases of the breast, concepts and clinical management. London: Bailliere Tindall, 1989
Classification of benign breast disorders The AND I classification based on physiological processes within the normal breast L E Hughes Department of Surgery, University of Wales College of Medicine, Cardiff, UK
Terminology in benign breast conditions has been confused by multiplicity of terms which do not relate accurately to clinical or histological patterns. Further confusion arises because terminology is not based on sound concepts of pathogenesis. The ANDI classification has been put forward as a nomenclature based on pathogenesis to replace the division of benign breast disorders into 'normal' and 'disease'. It recognizes that a spectrum exists for most conditions which extends from normal, through mild abnormality—'aberrations'—to disease. This classification allows precise definition of an individual patient problem in terms of pathogenesis, histology and clinical implications. It has proved helpful in deciding rational clinical management and in teaching the significance of benign breast disorders.
Attitudes to benign breast conditions have changed radically in recent years. Classically they have been considered only in relation to die need to exclude malignancy, other aspects have often been regarded as psychosomatic. Now the more severe manifestations are accepted as a significant cause of morbidity, yet less severe symptoms are so common that they must be regarded as lying within the range of normality. It is this fact that benign conditions may both lie within the range of normality or reflect severe disease which has caused great conceptual problems. Nomenclature has not kept up with the pace of change. Fibro-
252
BREAST DISEASE
cystic disease (histological terminology) continues as the term used for the clinical syndrome of premenstrual pain and nodularity. It was unfortunate that early workers noted many histological patterns in biopsies of breast nodules including fibrosis, cyst formation, epithelial hyperplasia and lymphocytic infiltration and assumed a causative relationship. As different workers placed differing emphases on minor aspects of these pathological changes, a wide variety of terms grew up. Early terms tended to reflect clinical concepts (e.g. chronic mastitis) but later they reflected histological appearances with terms such as hyperplastic cystic disease, fibroadenosis, fibrocystic disease etc. Since the term hyperplasia tends to be linked in the minds of clinicians with cancer, the use of this term often leads to an unwarranted association between 'fibrocystic disease' and cancer. The changed attitudes of recent years have arisen from in depth studies which have defined clinical syndromes more precisely, and endocrine studies which have provided a physiological basis for painful nodularity. RECOGNITION OF THE NORMALITY OF MUCH BENIGN BREAST 'DISEASE' In the 1960s a number of seminal studies demonstrated that the changes commonly described as fibroadenosis were widely distributed in patients who had not claimed to be symptomatic or demonstrated overt disease. There were two outstanding British examples. Parks1 showed, from studies of both surgical and autopsy specimens, a complete gradation between normal histology and disease; for example between developing lobules and fibroadenomas and between involuting lobules and macroscopic cysts. He also showed that epithelial hyperplasia is so common around the menopause as to be regarded as normal and that these lesions—so often regarded as indicative of cancer risk—could regress without treatment. In the second, Sandison2 showed from an extensive autopsy study that most of the changes previously regarded as disease are so common that they must be regarded as lying within the spectrum of normality. Other workers have confirmed these findings, and recently the concept has been taken further by proposing fibrocystic disease to be a 'non-disease'.3 While this concept may be of value in dispelling the supposed association between benign conditions and cancer, to regard it as a non entity is of little help
ANDI NOMENCLATURE
253
in the clinical management of those patients who have severe symptoms. Studies in Cardiff over the past 20 years have shown the high incidence of painful nodularity—approximately 50% of patients presenting to a breast clinic and two thirds of a population of working women report mastalgia. The clinical significance of mastalgia was quantified in the Cardiff Mastalgia Clinic where a classification was proposed,4 and the impact on patients lives assessed by means of breast pain charts and visual linear analogue scales. While most patients with breast pain were concerned with cancer and can be managed by adequate reassurance, mastalgia was found to be sufficiently severe in a minority to act as a major interference with quality of life and to be regarded as 'disease'. In its severe forms, it is associated with demonstrable endocrine abnormalities5 but not with specific histological patterns. It responds to appropriate therapy in a non-placebo fashion.6 NEED FOR A NEW NOMENCLATURE Thus is was becoming clear that any nomenclature should describe symptomatology, histological patterns and endocrine processes accurately and meaningfully in terms of pathogenesis, and be able to cover a spectrum from normality to severe disease. Review of earlier nomenclature showed that existing problems related to four main areas—the wide variety of terms in use, (more than 40 synonyms have been used for painful nodularity), the border-line between normal and abnormal, correlation of clinical symptoms and signs with histological changes and the assessment of premalignant potential. The border-line between normal and abnormal needs to be denned in terms of symptomatology as well as histology. Cyclical menstrual changes superimposed on the broader changes of breast development, pregnancy and involution lead to a wide spectrum of breast symptoms and of histological patterns. It is obviously important to try to define the point at which the limits of normality merge into abnormality. This is best done in terms of incidence and clinical impact. If present in a large majority of women both symptoms and histological patterns must be regarded as normal. Clinical impact is assessed in terms of quality of life or malignant potential. As mechanisms of pathogenesis become better understood, it may be possible to improve on our present attempts to define abnormal physiological parameters.
254
BREAST DISEASE
Unwarranted correlation of clinical with histological patterns has arisen because a causal relationship has been assumed with histology when a clinical area of nodularity has been biopsied. While the pathology of a fibroadenoma or cyst clearly correlates with the clinical finding, the same is not true for nodularity, which has no constant underlying histological abnormality. The use of the term hyperplasia has frequently led to an implication of premalignancy. Only since the high incidence of hyperplastic changes in normal breast tissue has been recognized has it been realized that hyperplasias must be denned much more precisely before they can be correlated with cancer risk, as elegantly shown by Page and his co-workers.7 It was against this background that the need was felt to develop a new nomenclature that would give a comprehensive framework into which individual conditions could be placed in a meaningful way in relation to clinical significance and management. Since most benign breast conditions arise on a background of the normal changes seen in relation to breast development, cyclical changes, pregnancy and involution, the normal processes within these periods of reproductive life have been used as the basis on which the nomenclature has been built. THE AND I CONCEPT These considerations lay behind the development of the AND I concept (Aberrations of Normal Development and Involution). This was first put forward to a national breast conference in Cardiff in 1982, and later published.8 A British working party was set up consisting of Surgeons, Radiologists and Pathologists, together with European and American representatives, and produced a final version (Table 1) which is awaiting formal publication. An example of the reasoning leading to this concept can be found in fibroadenoma—conventionally considered to be a benign tumour. Parks' work1 showed a full spectrum between normal lobules, large lobules which cannot be differentiated histologically from fibroadenomas, and clinical fibroadenomas. Hence subclinical fibroadenomas are much commoner than clinical ones. Fibroadenomas show features different to most benign tumours. Growth is not progressive, most fibroadenomas reach a size of 1-2 cm and then remain static. If pregnancy supervenes they lactate, showing greater hormone dependence than typical benign tumours. Finally, those that persist to the menopause regress leav-
Table 1 Aberrations of normal development and involution Aberration Stage (peak age in yrs)
Normal process
Early reproductive period (15-25)
Disease state Clinical presentation
Lobule formation
Fibroadenoma
Discrete lump
Stroma formation
Juvenile hypertrophy
Excessive breast development
Mature reproductive period (25-40)
Cyclical hormonal effects on glandular tissue and stroma
Exaggerated cyclical effects
Cyclical mastalgia and nodularity generalised or discrete
Involution (35-55)
Lobular involution (including microcysts, apocrine change fibrosis, adenosis)
Macrocysts
Discrete lumps
Sclerosing lesions
X-ray abnormalities
Ductal involution (including periductal round cell infiltrates)
Duct dilatation
Nipple discharge
Periductal fibrosis
Nipple retraction
Mild epithelial hyperplasia
Histological report
Epithelial turnover
Giant fibroadenoma Multiple fibroadenomas
Periductal mastitis with bacterial infection and abscess formation
ANDI N OMENCLA
Underlying condition
Epithelial hyperplasia with atypia to
256
BREAST DISEASE
ing a fibrous mass which may calcify. All these attributes are better considered as an aberration of normal lobular development than a pathological tumour. The spectrum of fibroadenoma extends from enlarged lobules (found histologically in most breasts), through to an aberration of normal lobular development (the clinical fibroadenoma), to disease, i.e. multiple or giant fibroadenomas. Two or 3 fibroadenomas are quite common—sufficient to still be regarded as an aberration—but 5 or more lesions are uncommon—so uncommon that they can be regarded as disease both from the point of view of rarity, the concern they cause the patient and the difficulty of management when a number of discrete fibroadenomas involve each breast. Similarly with size, although most fibroadenomas are only 1 cm or so in diameter, 2 or even 3 cm lesions are sufficiently common to be regarded as an aberration. But lesions of 5 cm or more are quite rare, and also behave differently. These giantfibroadenomasusually show continuing growth, and so become a management problem. They can best be regarded as disease, again both from the point of view of rarity and the problems they cause the patient. So, now it is possible to look at AND I (Table 1) as a two dimensional classification. The vertical dimension reflects the reproductive periods—breast development, cyclical change and involution—while the horizontal element covers the spectrum from normality through aberration to disease. Also included in the horizontal element, the clinical presentation is given its own column to emphasize that histological and clinical aspects correlate for some conditions, in others they do not. By using this two dimensional approach most of the common benign conditions of the breast can be fitted into this framework. A full explanation and description of the concept is given elsewhere.9 Its value must be judged in relation to its usefulness in conveying concepts of pathogenesis, and in management by encouraging the definition of the point along the spectrum where a clinical presentation lies. IMPLICATION FOR THE MANAGEMENT OF BENIGN BREAST DISORDERS This concept implies that most benign breast disorders can be regarded as no more than aberrations of normal processes and hence do not call for active specific treatment. Increasingly this is becoming accepted—as an example is the trend towards conservative management of fibroadenoma—a concept which follows auto-
ANDI NOMENCLATURE
257
matically from the ANDI classification. Management now becomes based on considerations such as accurate diagnosis, patient concern and interference with quality of life, rather than on the need to treat a disease. REFERENCES 1 Parks AG. The microanatomy of the breast. Ann R Coll Surg Engl 1959; 25: 235-251 2 Sandison AT. An Autopsy Study of the Human Breast. Natl Cancer Inst Monogr 8. Washington: US Department of Health Education and Welfare, 1962 3 Love SM, Gelman RS, Silcn W. Fibrocystic 'disease' of the breast—a nondisease. N Engl J Med 1982; 307: 1010-1014 4 Preece PE, Hughes LE, Mansel RE, Baum M, Bolton P, Gravelle IH. Clinical Syndromes of Mastalgia. Lancet 1976; ii: 670-673 5 Kumar S, Mansel RE, Hughes LE, Edwards CA, Scanlon MF. Production of response to endocrine therapy in pronounced cyclical mastalgia using dynamic tests of prolactin release. Clin Endocrinol 1985; 23: 699-704 6 Pye JK, Mansel RE, Hughes LE. Clinical experience of Drug Treatments for Mastalgia. Lancet 1985; ii: 373-7 7 Dupont WD, Page DL. Risk factors for breast cancer in women with proliferative disease. N Engl J Med 1985; 312: 146-151 8 Hughes LE, Mansel RE, Webster DJT. Aberrations of normal development and involution (ANDI). A new perspective on pathogencsis and nomenclature of benign breast disorders. Lancet 1987; (?): 1316-19 9 Hughes LE, Mansel RE, Webster DJT. Benign disorders and diseases of the breast, concepts and clinical management. London: Bailliere Tindall, 1989
