DISEASE

a resource handbook for health care providers

BREAST

Ontario Breast Cancer Information Exchange Project

BENIGN BREAST DISEASE

Fibrocystic Condition Fibroadenoma Mastalgia Nipple Discharge

A resource handbook for health care providers

Ontario Breast Cancer Information Exchange Project

Funding for the OBCIEP is provided by the Disease Prevention Division, Systems for Health Directorate, Health Promotion and Programs Branch, Health Canada. Copyright 1996 by Ontario Breast Cancer Information Exchange Project Toronto, Ontario Canada All rights reserved. No part of this publication may be reproduced, stored in a retrieval system, or transmitted, in any form, or by any means, electronic, mechanical, photocopying, recording, or otherwise, without prior written permission of the author. PRINTED AND BOUND IN CANADA For more information about the Ontario Breast Cancer Information Exchange Project, contact: 2075 Bayview Avenue Toronto, Ontario M4N 3M5 telephone: (416) 480-5899 fax: (416) 480-6002 email: obciep@octrf.on.ca

ACKNOWLEDGEMENTS

This booklet was developed by the Ontario Breast Cancer Information Exchange Project (OBCIEP). Its production required the efforts of many people. Working Group Pamela Chart, M.D. Brad Petrisor, Medicine Year II Boyd Academy Faculty of Medicine University of Toronto Karen Deane, RN, MN Natalie Parry, MHSc Reviewers G. Taylor, M.D. Family physicians in the Woodstock and Toronto area Graphic Design and Art Work Elijah Beckford Robin Carby S. E. Tulk, M.D.

CONTENTS

INTRODUCTION FIBROCYSTIC CONDITION

Incidence Etiology Pathology Presenting Symptoms Diagnosis Management Risk of Breast Cancer

1 3

FIBROADENOMA
Incidence Etiology Pathology Presenting Symptoms Diagnosis Management Risk of Breast Cancer

15

MASTALGIA
Incidence Etiology Pathology Presenting Symptoms Diagnosis Management Risk of Breast Cancer

23

NIPPLE DISCHARGE
Incidence Etiology Pathology Presenting Symptoms Diagnosis Management Risk of Breast Cancer

33

REFERENCES

39

INTRODUCTION

The Ontario Breast Cancer Information Exchange Project (OBCIEP) is one of five projects funded by Health Canada. Our mandate is to facilitate easy access to information about breast cancer and other related concerns for women, their families, and health care providers. In 1994-95, the OBCIEP conducted a series of needs assessments to identify areas of concern related to available information on breast disease and breast cancer.11 Those sampled included family physicians, breast surgeons, and nurses. Based on the findings, a need for information related to benign breast disease was evident. In response, this booklet has been developed. Four types of benign breast conditions are described in this booklet: fibrocystic condition, fibroadenoma, mastalgia, and nipple discharge. Information related to the incidence, etiology, pathology, presenting symptoms, diagnosis, management, and risk of breast cancer will be provided for each condition. This booklet is intended to be used as a resource for health care providers as well as a teaching tool for their patients. Diagrams are provided for easy explanation and a breast pain chart is available to photocopy. To obtain copies of the referenced articles, call the Cancer Information Service at 1-888-939-3333.

FIBROCYSTIC CONDITION

Fibrocystic breast condition (FCC) is characterized by nodularity of the breast tissue, accompanied by pain or tenderness. FCC affects a large number of women during their reproductive years.

INCIDENCE FCC is a common disorder. It has been reported to occur in 25% to 50% of women during reproductive life. Because of the ubiquitous nature of the symptoms, controversy exists over the labelling of this condition as a disease. FCC is the most common cause of breast lumps and breast complaints in pre-menopausal women. Although FCC is less frequently seen in women under 30 or over 55 years of age, symptoms can occur from the middle 20s through menopause.4 Figure 1 shows, that in comparison with the agespecific incidence of breast cancer, which increases as women age, the symptoms of FCC regress after menopause. However, post-menopausal women on hormone replacement therapy may continue to experience symptoms of FCC.

Figure 1: Comparison of Age-Specific Incidence of Breast Cancer and Fibrocystic Condition

Rate per 100,000

400 350 300 250 200 150 100 50 0 5 10 15 20 25 30 35 40 45 50 55 60 65 70 75 80 85+

Age Group

Incidence of fibrocystic condition

Source: Canadian Centre for Health Information, Statistics Canada, (1993).

ETIOLOGY Although the precise cause of FCC is unknown, several theories attempt to explain the etiology. These theories range from hormonally-mediated explanations to implications of diet.10,14 Hormone theories are supported by the bilateral nature of cysts and the relationship of cysts to menopause.4 The role of diet has been studied in relation to methylxanthines, such as caffeine found in food and drugs. The role of methylxanthines remains controversial. However, researchers have found that abstinence from methylxanthine

nodularity, pain, and tenderness in many of the women.10 In a study of theophylline, a methylxanthine used in the treatment of asthma, an increase severity of FCC symptoms was noted. This effect was seen to be additive if caffeine was also ingested.18

PATHOLOGY Breast tissue is described according to changes in the epithelial, ductal, and stromal tissues. Slide 1 illustrates the histological changes of FCC. The criteria for diagnosing FCC include: stromal fibrosis cystic dilatation of glands and ducts adenosis apocrine metaplasia epithelial hyperplasia.

Slide 1: Fibrocystic Condition

Three stages are apparent in the clinical pathological development of FCC. The first stage affects women in their 20s and is characterized by stromal fibrosis and proliferation.4,7 The second stage occurs in women during their 30s. It is distinguished by marked proliferation and hyperplasia of ducts, ductules, and alveolar cells. Multiple breast nodules may be accompanied by premenstrual breast pain and tenderness.6,19

The third stage is marked by development of solitary or multiple macrocysts in women during the late 30s and 40s. Cysts are mobile and can be discrete, palpable, and tender. A cluster of cysts can mimic a breast cancer mass. Patients in the third stage may experience sudden pain with point tenderness related to development of a cyst.6

PRESENTING SYMPTOMS Fibrocystic condition symptoms include: pain tenderness lumps lumpiness nipple discharge. The most common symptoms presented are bilateral pain and tenderness, especially in the upper outer quadrant, with accentuation during the premenstrual phase of the normal cycle.3,4 Pain or tenderness resulting from FCC may be most obvious in one quadrant of one breast or can be diffuse.3,7 The lump or lumpiness is caused by the glandular nature of breast tissue and the presence of underlying cysts. Cysts may vary considerably in size from tiny to over 6cm. Cysts are mobile, smooth, discrete structures which may be tender and firm.2 Solitary or multiple cysts may appear suddenly with rapid increase or decrease in size.4 Cysts and the associated pain may cause patients great anxiety related to the possibility of breast cancer. Nipple discharge may occur in 20% to 40% of women with FCC.7 This usually presents as a small amount of fluid from the nipple, provoked by milking the breast or squeezing the

underlying nipple areolar area. Nipple discharge is not normally spontaneous. Discharge emanates from multiple ducts and is usually bilateral. The colour of the discharge may vary from straw-like to dark brown or green. Predisposing factors associated with FCC include: nulliparity history of spontaneous abortions women who do not use oral contraceptives late menopause high socioeconomic status.4,7 Symptoms are often more pronounced late in reproductive life, prior to the onset of menopause.

DIAGNOSIS An essential first step is a systematic clinical breast examination with recording of important findings. Diagnostic investigations which support the clinical diagnosis of FCC include mammography, ultrasound, and cyst aspiration. Mammography The importance of mammography is to exclude the co-existence of breast cancer. Mammography is generally not recommended for women who are under 30 years of age, who are pregnant, or lactating. Mammography is of limited value in women with young, dense breast tissue. In addition, it is wise to avoid unnecessary exposure of young breasts to diagnostic radiation.

Mammographic signs of FCC include macrocysts which are usually multiple and bilateral, as shown in Slide 2. Macrocysts appear as rounded densities which may be discretely defined, partially obscured by surrounding parenchyma, or have invisible margins.9

Slide 2: Mammography Demonstrating Bilateral Macrocysts

Ultrasound Ultrasound is not a good technique for breast cancer screening. However, ultrasound is useful to demonstrate cysts, as shown in Slide 3. It can also differentiate between cysts and solid lumps.

Slide 3: Ultrasound Demonstrating a Cyst

Ultrasound examinations should be done at a facility where mammography is also offered, as these techniques are complementary. Cysts may be aspirated under ultrasound guidance.

A negative ultrasound in the presence of a palpable mass means the lesion is solid. Cyst Aspiration If the lesion can be trapped between two fingers, cyst aspiration can be performed as an office procedure, without local anaesthetic. Fluid aspirated from cysts can provide information about how long the cysts have been present, relieve tenderness, and be used for cytological evaluation. The colour of the fluid changes from straw to dark green as cysts age. Dark red fluid may indicate a recent trauma or possible malignancy. Fluid should be sent for cytology if bloody or if the cyst recurs. Fine Needle Aspiration Biopsy A fine needle aspiration biopsy may be considered when a solid breast lump or dominant thickening presents. It is recommended that this be done by a breast surgeon with dedicated cytopathological back-up.

MANAGEMENT Communication Reassurance of FCCs benign nature will decrease worry about the risk of breast cancer. Information about modification to diet may help alleviate symptoms. Dietary recommendations include: avoiding consumption of methylxanthines (e.g., caffeine in coffee, tea, cola, chocolate, and aged cheese) reducing dietary intake of fats lowering salt use avoiding tobacco.13

Figure 2: Cyst Aspiration

Medications Analgesics are prescribed for mild symptoms. For more severe pain, see the section on mastalgia. Surgery Surgical consultation should be obtained where a tissue diagnosis is required. Excisional breast biopsy is indicated when there is: a dominant lump even with negative mammographic results when a cyst is not demonstrated on ultrasound or aspiration suspicious mammographic lesions even with no clinical abnormalities.
11

RISK OF BREAST CANCER The overwhelming majority of patients with FCC can be confidently reassured about the lack of increased risk of breast cancer. Where surgical consultation and subsequent biopsy has been performed the following data, by Dupont and Page (1985), should be considered. They reported on 10,366 benign breast biopsies from a 17-year follow-up period. Non-proliferative disease represents no increased risk of developing breast cancer, as shown in Table 1. Table 1: Non-Proliferative Disease (NPD) Biopsies
(Dupont & Page, 1985)
Sample Data NPD NPD without a family history of breast cancer NPD with a family history of breast cancer Relative Risk (RR) 0.89 0.86 Confidence Interval (95%) 0.62 - 1.3 0.59 - 1.3

1.2

0.43 - 3.1

Proliferative disease without atypia (PDWA) was found in 26% of biopsies. Patients with PDWA were found to have a slight (two-fold) increased risk of breast cancer, as shown in Table 2. Diagnoses in this category included intraductal papilloma, radial scar, sclerosing adenosis, and moderate or florid ductal hyperplasia of the usual type.16 Patients with PDWA and a family history had a higher risk (RR = 3.2) of developing breast cancer.

12

Table 2: Proliferative Disease Without Atypia (PDWA) Biopsies

(Dupont & Page, 1985)
Sample Data PDWA PDWA without a family history of breast cancer PDWA with a family history of breast cancer Relative Risk (RR) 1.9 1.7 Confidence Interval (95%) 1.6 - 2.3 1.4 - 2.2

3.2

2.1 - 4.9

Proliferative disease with atypical hyperplasia (AH) occurred in 4% of biopsies. Diagnoses included both atypical ductal hyperplasia and atypical lobular hyperplasia. Patients with atypical hyperplasia had a substantial increase in risk for subsequent breast cancer, as shown in Table 3. Women with AH were at approximately a five-fold higher risk than the general population for developing breast cancer. Women with atypical hyperplasia and a family history of breast cancer appear to be at the greatest risk (RR = 8.9).16 Table 3: Proliferative Disease With Atypical Hyperplasia (AH) Biopsies (Dupont & Page, 1985)
Sample Data AH AH without a family history of breast cancer AH with a family history of breast cancer Relative Risk (RR) 4.4 - 5.3 3.5 Confidence Interval (95%) 2.3 - 5.5

8.9

4.8 - 17

13

FIBROADENOMA

Fibroadenoma is a common, benign breast condition presenting as one or more discrete, mobile nodules.

INCIDENCE Fibroadenomas are the most common cause of a breast lump for women in the 20 to 30 year age group. There is a decline in the incidence of fibroadenomas as women age.4 Fibroadenomas may be multiple and occur bilaterally in 12% to 16% of cases.7,23

ETIOLOGY Fibroadenoma is considered to be an abberation of the normal process of lobule development and involution rather than a true benign tumour.8,26 This is supported by the following facts. Fibroadenomas develop from a single lobule and not a single cell. Fibroadenomas closely resemble hyperplastic lobules seen in normal breasts. Fibroadenomas show the same hormonal dependence as normal breast tissue.4 The etiology of fibroadenoma is not precisely known. Research implicates an estrogen/progesterone imbalance.38
15

Fibroadenomas are more hormonally responsive than most benign tumors, demonstrating hormone dependence during both the menstrual cycle and pregnancy.8,23 An association between oral contraceptive use and a slight decreased incidence of fibroadenomas in pre-menopausal women provides support for the hormone imbalance assumption.20

PATHOLOGY Fibroadenoma is a biphasic neoplasm of stromal and glandular elements, as depicted in Slide 4. Simple fibroadenomas are a result of proliferation of underlying stromal components that may expand, stretch, or compress ductal epithelial tissue.2,7 This appears to be an innocuous overgrowth of fibrous tissue containing epithelial elements.20

Slide 4: Pathology of a Fibroadenoma

Complex fibroadenomas are described as those containing cysts, sclerosing adenosis, epithelial calcifications, or papillary apocrine changes.17 As shown in Slide 5, a fine needle aspiration biopsy illustrates the cytologic components of a fibroadenoma. They include: numerous, free-lying, oval, naked nuclei large, flat, branching sheets of uniform ductal epithelial cells high cellularity stromal fragments.28
16

Slide 5: Fine Needle Aspiration Biopsy of a Fibroadenoma

PRESENTING SYMPTOMS Patients frequently present with a single lump, usually 1cm to 2cm in size, which becomes more noticeable in the second half of the menstrual cycle.20,21,23 Fibroadenomas are discrete, mobile, non-tender, rounded or lobulated, and have a firm or rubbery texture.2,7 They may occur anywhere in the breast, however, the majority are located in the upper outer quadrant.23 The clinical behaviour of fibroadenomas may vary. They may grow up to 3 cm, stabilize during the reproductive years, and regress with age or menopause. During regression, they tend to become a small fibrotic mass with characteristic calcification recognized on mammography.8 Dent and Cant (1989) studied 201 fibroadenomas in a sample of 63 women. As shown in Figure 3, the fibroadenomas behaved in the following ways, over a 13 to 24 month period: 31% resolved 12% became smaller 25% remained the same 32% grew. Rarely fibroadenomas behave aggressively (e.g., juvenile or giant fibroadenomas).

17

Figure 3: Pie Chart of Fibroadenoma Behaviour

(Dent & Cant, 1989)

DIAGNOSIS Clinical Breast Examination Careful clinical breast examination (CBE) and documentation of findings are important in the management of fibroadenomas. Ultrasound Ultrasound is a useful tool, especially for women under 30 years of age. Sonography can accurately demonstrate the size of a well-defined lesion, identify the possibility of multiple lesions, and provide follow-up information on growth of a fibroadenoma. Mammography In older women, mammography is helpful in providing a definitive diagnosis of fibroadenoma. A low density, well-delineated nodule that has characteristic "popcorn" calcification, typical in the older age group, is shown in Slide 6.

18

MANAGEMENT Communication Management of fibroadenoma varies between observation and excision. Clinical considerations include patient needs, concerns, and expectations. Understanding the patient's needs will allow the clinician to provide meaningful, accurate information to a patient concerned about her breast lump. Reassurance, including a thorough explanation of the natural course of fibroadenoma, will allay anxiety and promote acceptance of conservative treatment. Breast Self-Examination Review breast self-examination (BSE) technique and provide BSE information. Pamphlets are available through your local unit of the Canadian Cancer Society and the Ontario Breast Screening Program (1-800-668-9304). Ultrasound Baseline ultrasound is appropriate for some younger women,with follow-up at two months, then at six months, to assess growth of a fibroadenoma. Core Biopsy Core biopsy establishes a definitive diagnosis. Subsequent growth or change is monitored by CBE. Core biopsy under ultrasound guidance reduces the need for excisional biopsy. Fine Needle Aspiration Biopsy FNAB should be followed by CBE to assess subsequent growth or change. Excisional Biopsy Excisional biopsy is appropriate when the patient finds the presence of the lesion unacceptable, if the fibroadenoma is greater than 2cm, or has demonstrated progressive growth.
20

RISK OF BREAST CANCER Although fibroadenomas are considered benign, the presence of ductal tissue means that malignancies may occur. The ductal epithelium of a fibroadenoma is subject to the same changes as breast epithelial tissue elsewhere, putting it at risk for malignant changes. Dupont et al. (1994) studied 2,458 breast biopsies diagnosed as fibroadenoma. Results showed a slight increased risk of breast cancer in patients with complex fibroadenomas. Atypical hyperplasia and a family history of breast cancer associated with a fibroadenoma may also increase the risk of developing breast cancer.

21

MASTALGIA

Mastalgia, or breast pain, is a common complaint frequently affecting pre-menopausal women.

INCIDENCE Mastalgia may affect up to 70% of women during their lifetime.36 Subjective perception and underreporting of breast pain make it difficult to assess the true incidence of mastalgia. Mastalgia has been reported in 45% to 66% of working women, while severe pain occurred in 15% to 21%.26,33 Breast pain is often categorized as cyclical, non-cyclical, or musculoskeletal. Experience in a mastalgia clinic setting found 67% of the women seen presented with cyclical mastalgia, 26% with non-cyclical mastalgia, and 7% with musculoskeletal pain.33

ETIOLOGY Numerous factors have been studied in relation to mastalgia including diet, prolactin levels, fluid retention, and altered proportions of fatty acid esters. However, the role of these elements has not been clearly established. Cyclical Mastalgia Although not precisely determined, the association of mastalgia with the menstrual cycle suggests a
23

hormonal origin. Supporting evidence, however, is inconsistent.7.29 Women with severe cyclical mastalgia have been found to more likely be pre-menopausal, nulliparous, or have a young age at first live birth than women with severe non-cyclical breast pain.33 Reduction in dietary fat intake has been shown to alleviate breast pain.30,34,35 In a study of women (n = 21) with persistent, severe mastalgia, subjects were randomized into a control group or an intervention group. The control group received general dietary advice while the intervention group were taught to reduce dietary fat intake to 15%. Blind assessment of mastalgia symptoms and review of patient diaries after six months demonstrated a significant reduction in symptoms including tenderness and swelling in the intervention group.30 Non-Cyclical Mastalgia Non-cyclical mastalgia is generally thought to be idiopathic. It may be associated with benign lesions such as fibrocysts, fibroadenomas, and duct ectasia.7 It is more refractory to treatment than cyclical breast pain. Musculoskeletal Pain Musculoskeletal pain refers to chest wall pain (e.g., costochondritis).26,29 PATHOLOGY No gross or histologic abnormalities specific to mastalgia have been determined.2,29 Infections of the breast usually result from pathogens from the skin.

24

PRESENTING SYMPTOMS Cyclical mastalgia is most commonly observed in women in their 30s.32 The pain, which lasts for a variable length of time, is frequently worse in the luteal phase of the menstrual cycle and resolves with menstruation.29,32 It is most often bilateral, but may be unilateral, and associated with diffuse nodularity.2,29 The extent of pain severity may differ with each menstrual cycle. Non-cyclical breast pain is often later in onset than cyclical mastalgia and unrelated to the menstrual cycle.29 It is often accompanied by nodularity and may be constant, intermittent, or sporadic in severity. The pain may be diffuse or localized to one area of one breast with possible radiation to the axilla or arm.7,29 Spontaneous resolution, after a variable period of time, usually occurs with both cyclical and non-cyclical mastalgia. Costochondritis may be localized to the costosternal junction or may be diffuse. Infection should be considered, when appropriate. Features of redness, swelling, pain, and increased temperature are usually obvious.

DIAGNOSIS Factors important in the evaluation of breast pain include: site type radiation timing of the pain with the menstrual cycle.

25

Clinical Breast Examination Diagnosis includes a thorough clinical breast examination to exclude an underlying disease process. Other conditions that need to be considered include: infection inflammatory breast cancer angina hiatus hernia cholelithiasis. Pain Chart Diagnosis of mastalgia involves documentation, using a breast pain chart for at least two months, as shown in Figure 4. This will enable the clinician to establish a pain pattern and determine its classification. Disruption of normal living, because of breast pain, should be recorded.36 Mammography Mammography may be appropriate for some women over 30 years of age whose breasts are difficult to examine.

MANAGEMENT Communication Reassurance of a benign condition is an important part of the management of mastalgia, particularly as spontaneous resolution usually occurs. Approximately 85% of women with breast pain will require no treatment once they receive reassurance of a benign condition. Relief from mild discomfort may be achieved through dietary changes (e.g., reduction in caffeine, salt, and saturated fat). The patient may benefit from wearing a sport bra or a supportive, well-fitting bra.2,36 Figure 5 illustrates a decision tree for use in the management of mastalgia.

26

Daily Breast Pain Chart

Record the amount of breast pain you experience each day by shading in each box as illustrated.

Severe Pain Mild Pain No Pain

For each example: if you get severe breast pain on the fifth of the month then shade in completely the square under 5. Please note the day your period starts each month with the letter "P"

Month

3 4

7 8

9 10 11 12 13 14 15 16 17 18 19 20 21 22 23 24 25 26 27 28 29 30 31

A sample of a breast pain chart, which would be used to assess pain, to determine the severity, duration and relationship of the pain to the menstrual cycle, and to assess response to treatment.

Figure 4: Holland, P.A., and Gateley, C.A. (1994)

27

Breast Self-Examination Review breast self-examination (BSE) technique and provide BSE information. Pamphlets are available through your local unit of the Canadian Cancer Society and the Ontario Breast Screening Program (1-800-668-9304). Medications Simple analgesics may alleviate mild mastalgia. Drug therapy is usually only advised for patients who experience severe pain, lasting for six months, that diminishes the quality of their lives.26 Discontinuation of oral contraceptive or hormone replacement therapy may reduce symptoms. Diuretics such as chlorothiazide have been used to alleviate mild to moderate pain. However, diuretics do not provide relief of severe pain or produce sustained benefit.14 The following medications are used to treat severe mastalgia. Evening Primrose Oil Evening primrose oil (Efamol) contains essential fatty acids that replace the metabolites thought to be deficient in women with mastalgia. Up to two 500mg capsules of evening primrose oil are prescribed three times a day.32,36 Response rates from 44% to 58% for women with cyclical mastalgia and 27% for women with non-cyclical mastalgia have been reported.26,29,32 Danazol Danazol is a pituitary gonadotropin inhibitor with antiestrogenic, antiprogestogenic, and androgenic properties.36 Danazol is thought to reduce follicle-stimulating hormone and luteinizing hormone levels. This results in lower estradiol production. In a dose of 100mg bid, danazol has been shown to produce a clinically useful response for breast pain and nodularity, especially for cyclical mastalgia.

28

Figure 5: Breast Pain Decision Tree

BREAST PAIN

CHEST WALL PAIN CHEST WALL PAIN exclude infection, inflammatory breast cancer, exclude infection, inflammatory breast angina, hiatus herina, cancer, angina, hiatus cholelithiasis hernia, mild analgesics prescribe cholelithiasis

MILD MASTALGIA MILD MASTALGIA

prescribe mild analgesics

clinical breast exam reassure benign condition reassurance dietary changes dietary changes supportive bra supportive bra mild analgesics mild analgesics

clinical breast exam

SEVERE MASTALGIA

Pain Chart (2 months)

Cyclical (80%)

Non-cyclical (10%)

reassurance changes dietary dietary changes bra supportive supportive analgesics mild bra mild analgesics hormone replacement discontinue discontinue hormone replacement diuretics evening primrose oil (Efamol) evening primrose oil (Efamol) danazol, bromocriptine danazol, bromocriptine participation in research studies participation in research studies

reassure benign conditions

29

A decrease in pain ranged from moderate, bearable, to complete resolution for 79% of women with cyclical mastalgia and 40% with non-cyclical mastalgia.33 If clinical effects are seen at two months, this dose may be reduced to 100mg daily, followed by a further reduction to 100mg every other day at four months.2,33 Side effects of danazol result from gonadotropin suppression and androgenic activity. They include weight gain, acne, hirsutism, menstrual irregularity, headache, nausea, and vomiting.33 The teratogenic potential of danazol requires effective contraception during treatment.26 Danazol is expensive and not frequently prescribed because of the side effects. Bromocriptine Bromocriptine is a dopamine agonist. It lowers pituitary levels of prolactin to reduce breast pain and nodularity. The efficacy of bromocriptine is equivalent to that of evening primrose oil. A clinical response, obtained in 54% of women with cyclical mastalgia and 33% with non-cyclical breast pain, supports its usefulness in cyclical mastalgia. Bromocriptine is given at bedtime with an initial dose of 1.25mg for the first week and 2.5mg for the following two months. The drug is continued for three months if a response occurs.2 Side effects of bromocriptine, for approximately 15% of patients, include nausea, vomiting, headache, giddiness, and postural hypotension.26,33 Side effects can be diminished by using an incremental dosage during the initial two weeks of treatment.32

30

Other Medications Other agents used for the treatment of mastalgia include Tamoxifen, Goserelin, Gestrinone, vitamin B6, iodine, and medroxyprogesterone, taken either orally or as a cream.37 However, the value of these treatments in managing breast pain remains undetermined.36 The dietary effect of flaxseed on mastalgia is currently under investigation.

RISK OF BREAST CANCER Mastalgia is not generally associated with malignant conditions. However, Preece et al. (1982) found that a small percentage (7%) of patients, from a sample of 240 subjects with operable cancer, presented with mastalgia alone. This pain was well-localized and persistent.

31

NIPPLE DISCHARGE

Nipple discharge is secretion from one or more mammary ducts appearing on the nipple. INCIDENCE Nipple discharge is not uncommon. It is reported in approximately 3% to 10% of patients with breast complaints.6,40,42 ETIOLOGY Nipple discharge may be seen in the following situations.40,41 Lactation Normal lactation is associated with pregnancy. Residual nipple discharge may last for several years following weaning from breastfeeding.6 Endocrine Disorders Thyroid and pituitary disorders or anovulatory syndrome can cause nipple discharge. Galactorrhea may result from pituitary or hypothalamic abnormalities, producing hyperprolactinemia (e.g., pituitary adenoma).43 Drug Side Effects Drugs which may cause galactorrhea include oral contraceptives, phenothiazines, methyldopa, cimetidine, tricyclic antidepressants, and

33

cannabis.6,43,45 Benign Breast Diseases Nipple discharge may be associated with benign breast diseases including intraductal papilloma, cystic disease, ductal ectasia, papillomatosis, and subareolar infections. Breast Cancer Occasionally, nipple discharge is the presenting symptom of breast cancer.

PATHOLOGY Nipple discharge is more often associated with benign rather than malignant conditions. When associated with duct ectasia, discharge stems from an increase in glandular secretion with production of an irritating fluid.43 Dilated and secretion-filled ducts in the subareolar tissue are seen that may or may not be accompanied by inflammation.2 Duct ectasia involves progressive inflammatory destruction of elastic ductal framework.31 When nipple discharge is associated with intraductal papilloma, the lesion is usually located within a major lactiferous duct in the subareolar region.2

PRESENTING SYMPTOMS Nipple discharge is often bilateral, arising from multiple ducts, and usually provoked by manual manipulation of the nipple or milking the breast.2,7

34

Nipple discharge may vary considerably in appearance. It can be milky, multi-coloured, purulent, clear or watery, yellow, dark greenish-black, serosanguinous, or sanguinous. Spontaneous nipple discharge appears with no manual manipulation. It may stain night clothing or undergarments. Women with spontaneous nipple discharge, on average, are five years older than women with provoked secretion.40 Galactorrhea presents as a bilateral, spontaneous, milky discharge that emanates from multiple ducts.43 Galactorrhea may commence in the second trimester of pregnancy and continue for several years after pregnancy and lactation.6 Case reports of bilateral bloody nipple discharge during pregnancy have indicated that spontaneous resolution occurs at or before parturition.42 The nipple discharge associated with duct ectasia is usually bilateral, comes from two or three ducts, and may be positive for occult blood in up to 50% of cases.41 Papillomas are most often seen between the ages of 40 and 60 years. They usually present as spontaneous, bloody nipple discharge from one duct of one breast, with or without a mass.

DIAGNOSIS There are two types of nipple discharge: physiological and significant. Significant nipple discharge is most often spontaneous, unilateral, and emanates from a single duct.2,7

35

Clinical Breast Examination A clinical breast examination should include an attempt to elicit the discharge by massaging each quadrant in turn. Document the following: colour presence of blood evidence of single or multiple ducts affected whether or not both breasts are involved. Cytology Cytological examination of nipple discharge should be requested (cytofix similar to pap smear) to examine for clumps of atypical or suspicious cells. A fat stain of galactorrhea will confirm the presence of milk.1,39 Prolactin levels should be obtained for positive stains.2 Hematest Hematest will demonstrate the presence of blood. Mammography Mammography should be considered in women suspected of having significant nipple discharge. It is not useful in women with galactorrhea. Galactography Galactography may be useful in localizing small intraductal papillomas. However, it cannot differentiate between benign and malignant lesions.43 Its role is limited since many breast surgeons will canalize the culprit duct at the time of surgery as a guide to excision.

36

MANAGEMENT Benign nipple discharge is characterized by the following factors: bilateral produced by squeezing the breast thick multi-coloured sticky. Further assessment is required for discharge that is: unilateral spontaneous persistent non-lactational contains blood.39 Communication Reassurance can be provided to patients without a breast mass, a negative mammography, and no evidence of an endocrine disorder. Spontaneous resolution often occurs in these patients. Patients should be encouraged to avoid stimulation of the nipple and breast. Breast Self-Examination Review breast self-examination (BSE) technique and provide BSE information. Pamphlets are available through your local unit of the Canadian Cancer Society and the Ontario Breast Screening Program (1-800-668-9304). Referral For patients suspected of having galactorrhea, endocrine referral is appropriate, especially if prolactin levels are elevated. Surgical consultation is necessary for patients

37

experiencing persistent discharge that is bloody, watery, serosanguinous, or serous. Breast Biopsy Breast biopsy is required for a nipple discharge which is bloody, unilateral, from a single duct, and accompanied by a mass.39 While most papillomas are benign, papillary carcinoma needs to be excluded. Subareolar exploration, to remove the involved ducts, is advised for patients with these complaints but no palpable mass. Surgical procedures include major duct excision or excision of the central nipple ducts. However, central duct excision is avoided, if possible, in young women or those interested in future pregnancies because it affects nipple sensation and breastfeeding ability.39

RISK OF BREAST CANCER Nipple discharge can be associated with malignancy or pre-cancerous lesions. Spontaneous, bloody, unilateral nipple discharge is associated with malignancy in 4% to 12% of cases.39 Bloody discharge is associated with higher rates of cancer. However, watery, serous, and serosanguinous discharges may also represent a considerable proportion of malignant diagnoses.7,43 Reports vary widely in the estimates of breast cancer related to nipple discharge.45,46 Papillomas with atypical hyperplasia (AH) have a higher relative risk (RR = 4 to 5 ) than those without AH, within or surrounding the papilloma.44 Factors associated with malignancy include a palpable mass and age over 50 years.40,44 The malignant lesion, resulting from nipple discharge, tends to be in situ carcinoma in almost half of

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REFERENCES

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7. Harris, J.R., Hellman, S., Henderson, I.C., & Kinne, D.W. (Eds) (1991). Breast Diseases. Second edition, J.B. Lippincott and Co., Philadelphia. 8. Hughes, L.E. (1991). Classification of benign breast disorders: The ANDI classification based on physiological processes. British Medical Bulletin, 47(2), 251-257. 9. Kopans, D.B. (1989). Breast Imaging. J.B. Lippincott Co., Philadelphia. 10. Minton, J.P., & Abou-Issa, H. (1989). Non-endocrine theories of the etiology of benign breast disease. World Journal of Surgery, 13, 680-684. 11. Ontario Breast Cancer Information Exchange Project. (1995). Informational needs about breast cancer and benign breast disease: Family Physicians, Breast Surgeons, and Nurses in Ontario.

FIBROCYCSTIC BREAST CONDITION 12. Baum, M. (1989). Benign breast disease: The cost of the service and the cost to the patient. World Journal of Surgery, 13, 669-673. 13. Borins, M. (1996). When the breasts are lumpy and painful. Patient Care Canada, 7(2), 61-65. 14. Dogliotti, L., Orlandi, F., & Angeli, A., (1989). The endocrine basis of benign breast disorders. World Journal of Surgery, 13, 674-679.

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15. Drukker, B.H., & deMendonca, W.C. (1987). Fibrocystic change and fibrocystic disease of the breast. Obstetrics and Gynecology Clinics of North America, 14(3), 685-702. 16. Dupont, W.D., & Page, D.L. (1985). Risk factors for breast cancer in women with proliferative breast disease. The New England Journal of Medicine, 312, 146-151. 17. Dupont, W.D., Parl, F.F., Hartmann, W. H., Brinton, L.A., Winfield, A.C., Worrell, J.A., Schuyler, P.A., & Plummer, W.D. (1994). Breast cancer risk associated with proliferative breast disease and atypical hyperplasia. Cancer, 71(4), 1258-1265. 18. Hindi-Alexander, M.C., Zielezny, M.A., Montes, N., Bullough, B., Middleton, E., Rosner, D.H., & London, W.M. (1985). Theophylline and fibrocystic breast disease. Journal of Allergy and Clinical Immunology, 75, 709-715. 19. Vorherr, H. (1986). Fibrocystic breast disease: Pathophysiology, pathomorphology, clinical picture, and management. American Journal of Obstetrics and Gynecology, 154(1), 161-179.

FIBROADENOMA 20. Canny, P.F., Berkowitz, G.S., Kelsey, J.L., & LiVolsi, V.A. (1988). Fibroadenoma and the use of exogenous hormones: A case control study. American Journal of Epidemiology, 127(3), 454-460. 21. Cant., P.J., Madden, M.V., Coleman, M.G. & Dent, D.M. (1995). Non-operative management of breast masses diagnosed as fibroadenoma. British Journal of Surgery, 82, 792-794.

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22. Conry, C. (1994). Evaluation of a breast complaint: Is it cancer? American Family Physician, 49(2), 445-450. 23. Dent, D.M., & Cant, P.J. (1989). Fibroadenoma. World Journal of Surgery, 13, 706-710. 24. Dupont, W.D., Page, F.F., Parl, F.F., Vnencak-Jones, C.L., Plummer, W.D., Rados, M.S., & Schuyler, P.A. (1994). Long-term risk of breast cancer in women with fibroadenoma. The New England Journal of Medicine, 331, 10-15. 25. Levi, F., Randimbison, L., Te, V.C., & Vecchia, C.L. (1994). Incidence of breast cancer in women with fibroadenoma. International Journal of Cancer, 57, 681-683. 26. Maddox, P.R., & Mansel, R.E. (1989). Management of breast pain and nodularity. World Journal of Surgery, 13, 699-705. 27. McCulloch, P., & George, W.D. (1990). Fibroadenosis, In: Smallwood, J.A. and Taylor, I. Benign Breast Disease. Edward Arnold, London, 59-65. 28. Stanley, M. L., Tani, E. M., & Skoog, L. (1990). Fine-needle aspiration of fibroadenomas of the breast with atypia: A spectrum including cases that cytologically mimic carcinoma. Diagnostic Cytopathology, 6(6), 375-382.

MASTALGIA 29. Belieu, R.M. (1994). Mastodynia. Obstetrics and Gynecology Clinics of North America, 21(3), 461-477.

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30. Boyd, N.F., McGuire, V., Shannon, P., Cousins, M., Kriukov, V., Mahoney, L., Fish, E., Lickley, L., Lockwood, G., & Tritchler, D. (1988). Effect of a low-fat, high-carbohydrate diet on symptoms of cyclical mastopathy. The Lancet, July, 128-132. 31. Deckers, P.J. & Ricci, A. (1992). Pain and lumps in the female breast. Hospital Practice, February, 67-94. 32. Gateley, C.A. & Mansel, R.E. (1991). Management of the painful and nodular breast. British Medical Bulletin, 47(2), 284-294. 33. Gateley, C.A., Miers, M., Mansel., R.E., & Hughes, L.E. (1992). Drug treatments for mastalgia: 17 years experience in the Cardiff mastalgia clinic. Journal of the Royal Society of Medicine, 85, 12-15. 34. Goodwin, P.J., Neelam, M., & Boyd, N.F. (1988). Cyclical mastopathy: A critical review of therapy. British Journal of Surgery, 75, Sept., 837-844. 35. Goodwin, P.J., DeBoer, G., Clark, R.M., Catton, P., Redwood, S., Hood, N., & Boyd, N.F. (1994). Cyclical mastopathy and premenopausal breast cancer risk: Results of a case control study. Breast Cancer Research and Treatment, 33, 63-73. 36. Holland, P.A., & Gateley, C.A. (1994). Drug therapy of mastalgia: What are the options? Drugs, 48(5), 709-716. 37. Peters, F. (1992). Multicentre study of gestrinone in cyclical breast pain. The Lancet, 339, 205-208.

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38. Preece, P.E., Baum, M., Mansel, R.E., Webster, D.J.T., Fortt, R.W., Gravell, I.H., & Hughes, L.E. (1982). Importance of mastalgia in operable breast cancer. British Medical Journal, 284, 1299-1300.

NIPPLE DISCHARGE 39. Donegan, W.L., Greene, F., & Love, S.M. (1990). Nipple discharge: Is it cancer? Patient Care, Jan., 79-96. 40. Gulay, H., Bora, S., Kilicturgay, S., Hamaloglu, E., & Goksel, H.A., (1994). Management of nipple discharge. Journal of the American College of Surgeons, 178, 471-474. 41. Hughes, L.E., (1991). Non-lactational inflammation and duct ectasia. British Medical Bulletin, 47(2), 272-283. 42. Lafreniere, R., (1990). Bloody nipple discharge during pregnancy: A rational for conservative treatment. Journal of Surgical Oncology, 43, 228-230. 43. Leis, H.P., (1989). Management of Nipple Discharge. World Journal of Surgery, 13, 736.-742. 44. Page, D.L., Salhany, K.E., Jensen, R.A., & Dupont, W.D. (1996). Subsequent breast carcinoma risk after biopsy with atypia in a breast papilloma. Cancer, 78(2), 258-266. 45. Seltzer, M.H., Perloff, L.J., Kelley, R.I., & Fitts, W.T. Jr. (1970). The significance of age in patients with nipple discharge. Surgical Gynecology and Obstetrics, 131, 519-522. 46. State, D. (1991). Nipple discharge in women: Is it cause for concern? Postgraduate Medicine, 89(3), 64-68.

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