PART VII. THERAPY
Therapy of Patients at Risk F. D. SKIDMORE” Dartford & Gravesend Hospitals Kent, England
I must confess to being puzzled by this title proposed by the Workshop organizers. If we are simply considering patients who present with the occasional acute noninflamed localized breast swelling which can be aspirated in the outpatient department then I am doubly concerned. Some patients present with an obvious breast cyst against a background of longstanding fibroadenotic breast lumpiness which shows the classical pattern of premenstrual augmentation and postmenstrual resolution. Cyclical mastodynia may also be part of the symptom complex. As I have shown in an earlier paper in this volume, breast cyst disease occurs in a crescendo pattern with the highest incidence being at the age of 48. Intrinsic and iatrogenic hormone factors have a close bearing on the mastodynia and premenstrual engorgement. From the iatrogenic standpoint the commonest hormone factor causing reactivation of breast pain and swelling in the late 40s is the administration of hormone replacement therapy by gynecologists or general practitioners. Another common cause of mastitis is the administration of Cimetidine (Tagamet) for the upper gastrointestinal symptom complex of epigastric pain, fat intolerance, and nocturnal reflux esophagitis. Ranitidine (Zantac) has recently shown to obviate this mastitis side effect.’ Who are the patients who are “at risk” of developing cyst disease? 1. Those patients who have had a previous cyst drained in the outpatient department. The British figures from Manchester and Dartford suggest that the average woman who presents with a breast cyst will have a total of 2.5 cysts before she is 54 years old. 2. There are certain patients whose breast cyst is not recognized as such in the outpatient department and who are therefore brought in to hospital for excision biopsy, during the course of which the cystic nature of the lesion is identified. Associated fibroadenotic tissue is usually sent for biopsy. 3. There are rare occasions when a biopsy is carried out for the correct reasons and where subsequently the report demonstrates the presence of coincident benign and malignant conditions. Such a lesion has to be treated on the basis of the type and extent of the malignant process, and the patient for practical purposes passes from the clinicians list of benign breast disease reviews to a 6monthly tumor review clinic.
‘Address correspondence to 109, Harley Street, London WIN IDG, England 284
SKIDMORE THERAPY OF PATIENTS AT RISK
285
PSYCHOTHERAPY Twenty-eight years ago Professor Verney and members of the Cambridge University Veterinary Anatomy Department demonstrated their early work on the hypothalmic-pituitary endocrine axis. This work has been continued with distinction by Professor Iversen in the MRC Neuro Endocrinology Unit at Cambridge and the staff of the Animal Physiology Research Unit at Babraham, United Kingdom. There can be no clinician in this room who is regularly dealing with benign breast disease who does not recognize the direct effect of psychological factors on breast pain, cessation of menstruation, and cessation of milk flow as a consequence of pituitary-mediated factors. Thus we see the look of relief on the patient’s face when a dreaded breast lump turns out to be a simple cyst. It is essential to counsel the patient after aspiration of the cyst. Mammography is mandatory and a warning should always be given that in the event of some untoward radiological finding we may well recommend early admission for excision biopsy of an impalpable lesion. This explanation can be best given if the mammography service runs in parallel with the breast clinic. My patients come back at the end of the clinic with their reported mammograms for a further discussion with the consultant surgeon as to the manner and timing of continuing care. I explain to the patient with a palpable residual lump or unsuspected contralateral or ipsilateral impalpable lump that early excision biopsy is indicated. These procedures are normally carried out as a day case under local or general anesthetic. Even if the woman does not have any radiologic abnormality on return to the clinic following aspiration, I go to some lengths to explain that the average woman has more than one cyst, and that these commonly occur in the premenstrual and premenopause stages. A cyst frequently develops when a period is missed in the run up to the menopause. All patients who have presented with a breast cyst are reminded that they have been listed for regular 6-monthly follow-up. Beyond this the patients have “open access” to my clinic insofar as they are encouraged to telephone my secretary if they have recurring breast pain or a new breast lump. Such patients are seen at the next breast clinic. I have come to the conclusion that this “open door” technique reduces the emotional anxiety of patients with a recurrent and sometimes painful breast swelling and makes them more willing to report symptoms and less anxious when they arrive at the clinic. Given my previous evidence to this workshop that 6% of women with breast cyst disease develop cancer by the age of 52 on the basis of a median 4-year follow-up no clinician running a breast clinic can afford to be complacent about recurrent symptoms in his patients.
MALIGNANT TRANSFORMATION What answer does one give to the patient with a breast cyst who asks whether the condition is a herald of subsequent cancer? I believe it is correct to tell patients that on the basis of the available evidence 5-6% of women with this type of benign disease will develop a breast cancer, but since both breasts are equally exposed to the prevailing hormonal milieu it is hardly surprising that the tumor may in fact arise in the opposite breast to the one in which a cyst was previously identified. The reasons
286
ANNALS NEW YORK ACADEMY OF SCIENCES
that I give for recommending biopsy for a breast lesion picked up on mammography in a woman who has previously had a breast cyst are as follows: 1. We have to accept that a field change in epithelial pattern can occur. 2. There are variants of benign disease ranging from the ultrabenign fibroadenoma to the more suspicious proliferative lesions such as epitheliosis, and lobular carcinoma in situ. 3. It should also be remembered that in recommending special assessment, mammography, and possibly biopsy to a woman with any form of a breast lump, one is effectively taking part in a public education exercise. The patient in discussion with female relatives, colleagues at work, or neighbors will hopefully reiterate the advice that the clinician has given, namely, that all breast lumps merit clinical and radiological assessment and biopsy. Who can tell what silent harm is done in society by a woman who has visited the breast clinic and who declaims to her friends that “nothing needs to be done.” This is not the way to expect to pick up early breast cancers in an at-risk population.
HORMONAL AVOIDANCE It is increasingly unusual in the United Kingdom to find women in their mid-40s who are still on the contraceptive pill. Most of the population in my area have rejected the thought of pregnancy after the age of 40.In stable relationships we therefore find that male vasectomy or female tubal ligation is common or alternatively because of anxiety about hypertension and risks of deep vein thrombosis women have turned to the coil as a means of long-term contraception. In this field however opinions are changing fast because of anxiety about cervical smear reports with a high incidence of inflammatory change. For the small percentage of women remaining on the pill when they present with breast cyst disease, my policy is to advise immediate discontinuation of the contraceptive pill and the use of mechanical barrier contraception. If the patient or her husband so wishes, arrangements can be put in hand for early male or female sterilization. We sometimes see patients where the pill is being used to treat menorrhagia. If patients present with increased breast activity and cyst disease in such circumstances, it is my policy to discuss the patient with my gynecological colleagues and arrange for the patient to have dilation and curettage at short notice.
HORMONE-REPLACEMENTTHERAPY My understanding of the natural biology of the human breast is that the organ was designed for a series of lactations during reproductive life. It was not designed to undergo (a) 300-400 menstrual cycles with 2 or 3 one year respites during pregnancies; (b) hormonal stoppage of lactation and pharmacological doses of estrogen and progesterone derivatives; or (c) a further hormone boost of a noncyclical nature
SKIDMORE: THERAPY OF PATIENTS AT RISK
287
at the menopause in order to prevent cardiovascular disease, osteoporosis, loss of libido, and skin wrinkles. Clinical evaluation of the breast in women who are receiving hormone-replacement therapy (HRT) is difficult because of a tendency to develop rather brawny bilateral upper outer quadrant fibroadenosis. The situation is complicated if the patient has a dysplastic mammogram because HRT will retard the normal process of breast glandular replacement by fatty tissue. However, patients themselves or in concert with their gynecologists may insist on continuing with HRT. The breast surgeon should make it clear that from his standpoint the penalty to the patient will be more frequent mammograms, early biopsy of suspicious lesions, and therefore augmented anxiety when it comes to differentiating new lesions from previous biopsy scar tissue. I note with interest that a two-day symposium is being held in London in June, 1989 on the subject of oral contraceptives and breast cancer. With regard to HRT and the risk of breast cancer, we may have to accept at present the Scottish legal verdict of “not proven. ” However, given that malignant conditions likely to be exacerbated by estrogen therapy including breast tumors are an absolute contraindication to such therapy, one can be pardoned for an attachment to the hypothesis that artificial hormonal reawakening of biological tissues whose allotted function has ended may carry an unacceptable delayed penalty of enhanced tumor incidence.
REFERENCE 1. BRADLOW, H.L. Personal communication.
Therapy of Patients at Risk F. D. SKIDMORE” Dartford & Gravesend Hospitals Kent, England
I must confess to being puzzled by this title proposed by the Workshop organizers. If we are simply considering patients who present with the occasional acute noninflamed localized breast swelling which can be aspirated in the outpatient department then I am doubly concerned. Some patients present with an obvious breast cyst against a background of longstanding fibroadenotic breast lumpiness which shows the classical pattern of premenstrual augmentation and postmenstrual resolution. Cyclical mastodynia may also be part of the symptom complex. As I have shown in an earlier paper in this volume, breast cyst disease occurs in a crescendo pattern with the highest incidence being at the age of 48. Intrinsic and iatrogenic hormone factors have a close bearing on the mastodynia and premenstrual engorgement. From the iatrogenic standpoint the commonest hormone factor causing reactivation of breast pain and swelling in the late 40s is the administration of hormone replacement therapy by gynecologists or general practitioners. Another common cause of mastitis is the administration of Cimetidine (Tagamet) for the upper gastrointestinal symptom complex of epigastric pain, fat intolerance, and nocturnal reflux esophagitis. Ranitidine (Zantac) has recently shown to obviate this mastitis side effect.’ Who are the patients who are “at risk” of developing cyst disease? 1. Those patients who have had a previous cyst drained in the outpatient department. The British figures from Manchester and Dartford suggest that the average woman who presents with a breast cyst will have a total of 2.5 cysts before she is 54 years old. 2. There are certain patients whose breast cyst is not recognized as such in the outpatient department and who are therefore brought in to hospital for excision biopsy, during the course of which the cystic nature of the lesion is identified. Associated fibroadenotic tissue is usually sent for biopsy. 3. There are rare occasions when a biopsy is carried out for the correct reasons and where subsequently the report demonstrates the presence of coincident benign and malignant conditions. Such a lesion has to be treated on the basis of the type and extent of the malignant process, and the patient for practical purposes passes from the clinicians list of benign breast disease reviews to a 6monthly tumor review clinic.
‘Address correspondence to 109, Harley Street, London WIN IDG, England 284
SKIDMORE THERAPY OF PATIENTS AT RISK
285
PSYCHOTHERAPY Twenty-eight years ago Professor Verney and members of the Cambridge University Veterinary Anatomy Department demonstrated their early work on the hypothalmic-pituitary endocrine axis. This work has been continued with distinction by Professor Iversen in the MRC Neuro Endocrinology Unit at Cambridge and the staff of the Animal Physiology Research Unit at Babraham, United Kingdom. There can be no clinician in this room who is regularly dealing with benign breast disease who does not recognize the direct effect of psychological factors on breast pain, cessation of menstruation, and cessation of milk flow as a consequence of pituitary-mediated factors. Thus we see the look of relief on the patient’s face when a dreaded breast lump turns out to be a simple cyst. It is essential to counsel the patient after aspiration of the cyst. Mammography is mandatory and a warning should always be given that in the event of some untoward radiological finding we may well recommend early admission for excision biopsy of an impalpable lesion. This explanation can be best given if the mammography service runs in parallel with the breast clinic. My patients come back at the end of the clinic with their reported mammograms for a further discussion with the consultant surgeon as to the manner and timing of continuing care. I explain to the patient with a palpable residual lump or unsuspected contralateral or ipsilateral impalpable lump that early excision biopsy is indicated. These procedures are normally carried out as a day case under local or general anesthetic. Even if the woman does not have any radiologic abnormality on return to the clinic following aspiration, I go to some lengths to explain that the average woman has more than one cyst, and that these commonly occur in the premenstrual and premenopause stages. A cyst frequently develops when a period is missed in the run up to the menopause. All patients who have presented with a breast cyst are reminded that they have been listed for regular 6-monthly follow-up. Beyond this the patients have “open access” to my clinic insofar as they are encouraged to telephone my secretary if they have recurring breast pain or a new breast lump. Such patients are seen at the next breast clinic. I have come to the conclusion that this “open door” technique reduces the emotional anxiety of patients with a recurrent and sometimes painful breast swelling and makes them more willing to report symptoms and less anxious when they arrive at the clinic. Given my previous evidence to this workshop that 6% of women with breast cyst disease develop cancer by the age of 52 on the basis of a median 4-year follow-up no clinician running a breast clinic can afford to be complacent about recurrent symptoms in his patients.
MALIGNANT TRANSFORMATION What answer does one give to the patient with a breast cyst who asks whether the condition is a herald of subsequent cancer? I believe it is correct to tell patients that on the basis of the available evidence 5-6% of women with this type of benign disease will develop a breast cancer, but since both breasts are equally exposed to the prevailing hormonal milieu it is hardly surprising that the tumor may in fact arise in the opposite breast to the one in which a cyst was previously identified. The reasons
286
ANNALS NEW YORK ACADEMY OF SCIENCES
that I give for recommending biopsy for a breast lesion picked up on mammography in a woman who has previously had a breast cyst are as follows: 1. We have to accept that a field change in epithelial pattern can occur. 2. There are variants of benign disease ranging from the ultrabenign fibroadenoma to the more suspicious proliferative lesions such as epitheliosis, and lobular carcinoma in situ. 3. It should also be remembered that in recommending special assessment, mammography, and possibly biopsy to a woman with any form of a breast lump, one is effectively taking part in a public education exercise. The patient in discussion with female relatives, colleagues at work, or neighbors will hopefully reiterate the advice that the clinician has given, namely, that all breast lumps merit clinical and radiological assessment and biopsy. Who can tell what silent harm is done in society by a woman who has visited the breast clinic and who declaims to her friends that “nothing needs to be done.” This is not the way to expect to pick up early breast cancers in an at-risk population.
HORMONAL AVOIDANCE It is increasingly unusual in the United Kingdom to find women in their mid-40s who are still on the contraceptive pill. Most of the population in my area have rejected the thought of pregnancy after the age of 40.In stable relationships we therefore find that male vasectomy or female tubal ligation is common or alternatively because of anxiety about hypertension and risks of deep vein thrombosis women have turned to the coil as a means of long-term contraception. In this field however opinions are changing fast because of anxiety about cervical smear reports with a high incidence of inflammatory change. For the small percentage of women remaining on the pill when they present with breast cyst disease, my policy is to advise immediate discontinuation of the contraceptive pill and the use of mechanical barrier contraception. If the patient or her husband so wishes, arrangements can be put in hand for early male or female sterilization. We sometimes see patients where the pill is being used to treat menorrhagia. If patients present with increased breast activity and cyst disease in such circumstances, it is my policy to discuss the patient with my gynecological colleagues and arrange for the patient to have dilation and curettage at short notice.
HORMONE-REPLACEMENTTHERAPY My understanding of the natural biology of the human breast is that the organ was designed for a series of lactations during reproductive life. It was not designed to undergo (a) 300-400 menstrual cycles with 2 or 3 one year respites during pregnancies; (b) hormonal stoppage of lactation and pharmacological doses of estrogen and progesterone derivatives; or (c) a further hormone boost of a noncyclical nature
SKIDMORE: THERAPY OF PATIENTS AT RISK
287
at the menopause in order to prevent cardiovascular disease, osteoporosis, loss of libido, and skin wrinkles. Clinical evaluation of the breast in women who are receiving hormone-replacement therapy (HRT) is difficult because of a tendency to develop rather brawny bilateral upper outer quadrant fibroadenosis. The situation is complicated if the patient has a dysplastic mammogram because HRT will retard the normal process of breast glandular replacement by fatty tissue. However, patients themselves or in concert with their gynecologists may insist on continuing with HRT. The breast surgeon should make it clear that from his standpoint the penalty to the patient will be more frequent mammograms, early biopsy of suspicious lesions, and therefore augmented anxiety when it comes to differentiating new lesions from previous biopsy scar tissue. I note with interest that a two-day symposium is being held in London in June, 1989 on the subject of oral contraceptives and breast cancer. With regard to HRT and the risk of breast cancer, we may have to accept at present the Scottish legal verdict of “not proven. ” However, given that malignant conditions likely to be exacerbated by estrogen therapy including breast tumors are an absolute contraindication to such therapy, one can be pardoned for an attachment to the hypothesis that artificial hormonal reawakening of biological tissues whose allotted function has ended may carry an unacceptable delayed penalty of enhanced tumor incidence.
REFERENCE 1. BRADLOW, H.L. Personal communication.
