15. | Principles of Surgery, Companion Handbook

Chapter 14 Breast

Principles of Surgery Companion Handbook

CHAPTER

14
BREAST

Embryology
Anatomy
Histology
Physiology
Gynecomastia
Diagnosis of Breast Disease
	Imaging Studies
Inflammatory and Infectious Disorders
Benign Lesions
Carcinoma of the Breast
	Staging of Breast Cancer
	Histopathology/Epidemiology
	Noninfiltrating Malignancies
	Infiltrating Malignancies
	Treatment
	Prognosis
	Carcinoma of the Male Breast
	Breast Cancer during Pregnancy and Lactation
	Rehabilitation

EMBRYOLOGY

In the sixth week of gestation, a mammary ridge, or “milk line,” appears in the embryo as an ectodermal thickening from each axilla to the groin. These ridges disappear except for a small area in the pectoral region. Anomalous persistence is often mistaken for nevi, and the aberrant breast tissue in the axilla or in the milk line may become prominent during pregnancy. The breast starts as an ingrowth of ectoderm as a primary “bud” with 15–20 secondary buds. These canalize in the last 2 months of gestation. In both newborn females and males, there is a transient breast enlargement secondary to increased levels of hormones crossed over from the maternal circulation. Several developmental abnormalities are noted, particularly in females, e.g., polymastia, polythelia, and accessory or ectopic mammary tissue.

ANATOMY

Except for mild hypertrophy during the neonatal period and puberty, the male breast undergoes little change throughout life. In females, the prepubertal “bud” develops from 11–15 years, and lobulation occurs after the first ovulation.

The adult female breast extends from the second to the sixth rib and from the sternal border to the anterior or midaxillary line. The glandular tissue base is circular in outline except for an extension to the axilla (tail of Spence). Cooper's ligaments help to suspend the glandular tissue from the deep layer of superficial fascia to the anterior superficial fascia immediately under the skin. The subareolar area and nipple contain smooth muscle that contracts with tactile or thermal stimulation.

Arterial Supply The breast is perfused by (1) perforating branches of the internal mammary artery (first through fourth interspaces) medially, (2) the lateral and highest thoracic arteries, pectoral branches of the acromiothoracic artery, and (3) lateral branches of the posterior intercostal arteries.

Venous Drainage Superficial subcutaneous veins drain into the internal mammary or neck veins; deep veins correspond with the arterial supply. Mammary cancer may metastasize to vertebral bodies or the pelvis, bypassing the lungs because of intercostal drainage to vertebral veins (Batson's plexus).

Lymphatic Drainage Even though there is some variation, six anatomic groups are identified, i.e., the lateral (axillary vein), external mammary, scapular, central, subclavicular, and interpectoral (Rotter) groups. Assigned “levels” refer to their relation to the pectoralis minor. Level I (lateral to pectoralis minor) includes the external mammary axillary vein and subscapular groups. Level II (deep to pectoralis minor) includes the central group. Level III (medially or above) includes the subclavicular nodes. Collected lymph drains into the thoracic duct before entering the venous system. About 75 percent of lymph from the breast passes through the axillary nodes, whereas the rest of it passes through the parasternal nodes. The medial part of breast also drains into the internal mammary (intrathoracic) set of nodes. The average number of lymph nodes harvested surgically is about 20 in axillary dissection.

HISTOLOGY

The breast is composed of 15–20 tubuloalveolar glands. They terminate into lactiferous ducts lined by columnar epithelium. A milk sinus in the subareolar region is lined by squamous epithelium and opens into the ampulla of the nipple.

PHYSIOLOGY

Development and function of the breast are initiated by various hormones but predominantly by estrogen, progesterone, and prolactin. Estrogen is known to stimulate development of the breast ducts. Progesterone initiates development of breast lobules as well as differentiation of epithelial cells. Prolactin stimulates lactogenesis in late pregnancy and the postpartum period.

Cyclic Change Breast volume is greatest in the second half of the menstrual cycle. Vascular congestion and lobular proliferation regress with menses.

Pregnancy and Lactation Alveoli and lobules proliferate as the ducts branch. The nipple and areola darken, and Montgomery's glands (of the areola) become prominent. Oxytocin and a suckling-induced surge of prolactin promote production and ejection of milk.

Menopause With decline in ovarian estrogen and progesterone, the lobules and ducts involute, and the volume is replaced by fat. This change renders the breast more amenable for diagnostic mammography in older women.

GYNECOMASTIA

Gynecomastia implies enlargement of male mammary tissue. Physiologic gynecomastia may be seen in the neonatal period, in adolescence, or in old age and almost always as a result of excess estrogens in relation to circulating testosterone. Generally, at least 2 cm of subareolar breast tissue must be present for the diagnosis of gynecomastia. Glandular and ductal structures enlarge, along with enlargement of stromal elements. Androgen deficiency in, for example, orchitis or testicular failure or estrogen excess as a result of testicular or nontesticular tumors may be associated with gynecomastia. Rarely, thyroid dysfunction, alcoholism, or drugs may induce similar change. Pubertal gynecomastia is generally unilateral, whereas senescent gynecomastia is bilateral.

Treatment Medical treatment is rarely successful. Biopsy may be necessary to confirm the diagnosis. Large, progressive gynecomastia may require subcutaneous mastectomy through a circumareolar incision.

DIAGNOSIS OF BREAST DISEASE

Presentation A lump, nipple discharge, pain, a change in contour, skin ulceration, and asymmetry are the usual features that make the patient seek medical consultation. Clinical history is important.

Clinical Examination Inspection Asymmetry, skin retraction, edema (peau d'orange), nipple inversion, and erosion are more easily detected with the patient seated, hands on hips and then elevated overhead.

Palpation With patient seated erect, supraclavicular and axillary fossae are examined, including the tail of Spence and central breast tissue. The entire breast is reexamined with the patient supine and arms overhead. The lateral part of the breast is examined with slight elevation of the ipsilateral side by a pillow. Features of importance of a lump or lymph node are its size, shape, mobility, consistency, and location, and these should be recorded on an outline diagram.

Workup Subsequent to clinical examination, the workup proceeds in an orderly progression (Table 14-1).

TABLE 14-1 PATHOPHYSIOLOGIC MECHANISMS OF GYNECOMASTIA

Imaging Studies

Mammography Used in North America since 1960, mammography has been refined in equipment and skilled interpretation. It delivers about 0.1 cGy of radiation per study. Mammography complements the clinical examination and history and enhances the diagnostic accuracy of breast diseases. It is generally indicated for screening in older women, for evaluation of a palpable mass, for follow-up examination after segmental mastectomy, or for evaluation of breasts that are difficult to examine clinically. It is therefore an important tool for early detection of (nonpalpable) occult cancer (<5 mm diameter) or multicentricity of disease. The presence of a clustered microcalcific, stellate density, a mass with irregular margins, skin thickening/retraction, or asymmetry may be suggestive of cancer. Screening mammography reduced the incidence of mortality by 33 percent in the Health Insurance Plan (HIP) study. Mammograms detected cancers early enough to be node negative in 80 percent of patients as compared with 50 percent detected only on clinical examination. The false-positive rate was 11 percent, and the false-negative rate was 6 percent. Current guidelines of the American Cancer Society recommend a “baseline” mammogram at 35 years of age and annual mammograms after 50 years of age. Between 40 and 50 years of age the patient should consult her physician. In a woman whose mother has a positive history of cancer, the screening is recommended 10 years earlier than the age of mother at the time of her diagnosis. Stereotactically guided and needle localization techniques of biopsy are used to obtain a tissue diagnosis in nonpalpable lesions. Ultrasonography is helpful in distinguishing solid from cystic lesions. Cyst aspiration or biopsy can be performed under ultrasound guidance. Ultrasound is not recommended as a screening tool, however. Doppler flow studies, light scanning, and thermography lack diagnostic sensitivity. Magnetic resonance imaging (MRI) has proved questionable thus far in routine use. Isotope scans (sestamibi, mira luma) using technetium-99m has shown very limited promise. Ductography (galactography), i.e., injection of radiopaque contrast material into mammary ducts, is performed in patients with spontaneous, persistent nipple discharge to identify intraductal pathology (papillomas) and, rarely, communicating cysts.

Biopsy/Fine-Needle Aspiration Tissue diagnosis is mandatory prior to initiation of definitive treatment. Palpable lesions can be aspirated easily with a fine needle (FNA) for cytologic diagnosis. FNA is reliable in 80–90 percent of patients. Correlation of clinical examination, mammogram, and cytology (“triple diagnosis”) enhances the accuracy to 95 percent. Core biopsy with a Tru-Cut needle, like the incisional/excisional biopsy, has higher diagnostic accuracy. Palpable cysts are treated by simple aspiration. Nonpalpable lesions generally suspected on mammography can be diagnosed with the help of stereotactic core biopsy or excised after a radiographically aided wire localization. Biopsy incisions should be made with cosmetic and subsequent surgical needs in view. Tissue is submitted for histology, hormone receptors, flow cytometry, and c-erbB-2 analysis if so desired. Staging workup is generally done before the definitive procedure.

INFLAMMATORY AND INFECTIOUS DISORDERS

Bacterial Infections Staphylococcus and Streptococcus are the most common organisms in breast abscesses. They are typically related to and seen in the first few weeks of lactation. Streptococcal infections generally are diffuse and associated with cellulitis and lymphangitis, whereas staphylococcal infections are more localized, with formation of an abscess or abscesses. Treatment with antibiotics, drainage, and local care generally is adequate. Puerperal mastitis is more serious when it is hospital acquired in contrast to the sporadic type. It requires antibiotic therapy in addition to local care with a breast suction pump and usually a transient interruption of breast-feeding.

Recurrent Periareolar Abscess Recurrent periareolar abscess generally is due to obstruction of the milk sinus as a result of squamous metaplasia of a lactiferous duct (SMOLD). Resection of the involved duct is indicated to prevent recurrence.

Hydradenitis Suppurative Hydradenitis suppurativa of areolar or axillary sebaceous glands may present as chronic or recurrent cutaneous abscesses—requiring excision of the involved skin.

Mondor's Disease Mondor's disease is a cordlike tender area of skin with linear indentation due to thrombophlebitis of the thoracoepigastric or lateral thoracic vein (“string thrombosis”). Only symptomatic treatment is needed because the process resolves spontaneously in about 6 weeks.

BENIGN LESIONS

After years of nomenclature controversies, Page and associates recommend that benign breast lesions be assigned to one of the three categories: (1) nonproliferative, (2) proliferative without atypia, and (3) proliferative with atypia. However, there are other benign lesions, such as adenomas and fibroadenomas.

Nonproliferative Lesions Nonproliferative lesions include fibrocystic change and microcalcifications related to epithelial changes. About 70 percent of biopsy specimens show these changes.

Proliferative Lesions without Atypia This category includes sclerosing adenosis, moderate hyperplasia, and intraductal papillomas. About 25 percent of biopsy tissues show these changes.

Proliferative Lesions with Atypia This category includes lobular and ductal lesions showing evidence of atypia in their nuclear morphology. These are generally confused with carcinoma in situ. The lesions have a higher risk of malignancy (4–5 times), especially in patients with a positive family history. Only 4 percent of biopsy specimens show these changes.

Fibrocystic Disease Better termed as fibrocystic mastopathy (or fibrocystic disorder), fibrocystic disease presents clinically as painful, irregular, and firm nodularities of the breast. It is generally more symptomatic in the second half of the menstrual cycle. Management includes restriction of caffeine and sometimes diuretics after basic clinical evaluation and, if necessary, mammography. Aspiration cytology and sometimes open biopsy may be required in suspicious lesions to rule out concomitant malignancy. Treatment with danazol (a synthetic androgen analogue) may become necessary in extremely symptomatic patients.

Cysts Cysts are areas of fluid accumulation varying in size from 1 mm to several centimeters. These are simply treated by aspiration. Excision or biopsy is indicated if the aspirate is bloody or a residual mass persists after aspiration.

Fibroadenoma Fibroadenoma presents as a firm, rubbery, painless, mobile, well-circumscribed mass, usually in younger women in the second or third decade of life. Fibroadenomas are slightly more common in African-Americans than in Caucasians. FNA is helpful in diagnosis. While excision is commonly recommended as the treatment of choice, some workers favor observing these lesions in patients under 25 years of age with benign cytology. Sclerosing adenosis is often an incidental finding but sometimes presents as a palpable mass. Occasionally, these lesions show calcifications on the mammogram.

Radial Scar Detected as a distorted fibrous density with microcalcifications on mammography, a radial scar often mimics malignancy. It usually requires biopsy to confirm the diagnosis.

Fat Necrosis Fat necrosis generally presents as a firm mass—sometimes with a preceding history of local trauma. In later stages of evolution, fat necrosis may present as an “oil cyst”—clearly distinguishable on mammography as a lucent area.

Papilloma Intraductal papilloma usually presents as spontaneous, unilateral, serosanguineus or bloody nipple discharge. Papillomas have tendency for development of carcinoma. About a third of patients with bloody nipple discharge have papilloma, and 20 percent have carcinoma. Sequential radial compression and ductography generally help to identify the involved duct, and excision is easily accomplished with a circumareolar incision.

Phyllodes Tumor This tumor presents as a large, bulky mass, sometimes mistaken for a large fibroadenoma. It is important to distinguish the common benign phyllodes tumor from its malignant variant. Treatment is controversial and varies from wide local excision to simple mastectomy.

CARCINOMA OF THE BREAST

Incidence Carcinoma of the breast is the most common malignant neoplasm in women, with a steady increase in incidence since 1940. The risk of breast cancer quickly surges during the child-bearing age (25–40 years) with a slower rise thereafter. In the 1970s, the probability of a woman developing breast cancer in the United States was 1 in 13; in 1980, 1 in 11; and in 1996, 1 in 8. Fortunately, however, in 1998, the trend seems to have plateaued. Even though the incidence in African-American women is lower, the 5-year survival rate is higher in white women—78 percent compared with 63 percent in blacks. This difference is generally attributed to earlier diagnosis in white women. Worldwide, England and Wales have the highest mortality from breast cancer (27 per 100,000 population) compared with the United States (22 per 100,000). South Korea has the lowest incidence of breast cancer (2.6 per 100,000).

Etiology Female gender itself is a predisposing factor, since only 1 percent of breast cancers occur in males.

Genetic Factors Henderson and Lynch have documented heredity and genetic predisposition for breast carcinoma and have suggested three categories: sporadic, familial, and hereditary breast cancers depending on the degree of familial association. Among these, 68 percent of cancers were sporadic, 23 percent were familial, and 9 percent were hereditary. Biomarkers such as BRCA1 and BRCA2, recently mapped to chromosomes 17 and 13, respectively, may indicate a woman's susceptibility to breast cancer.

Hormone Use While most studies indicate no increased incidence of breast cancer with the use of oral contraceptives, Lipnick and colleagues noted some adverse effect if oral contraceptives were taken at an early age or before the first full-term pregnancy. Also, hormone replacement therapy in perimenopausal and postmenopausal women may slightly increase the risk of breast cancer. Obesity and a history of irradiation to the breast area also may increase the risk of breast cancer.

Breast-Feeding and Menopause The validity of the protective role of breast-feeding now is under question. Later menopause is associated with a higher risk of breast cancer, presumably due to more years of exposure to estrogens.

Infertility/Nulliparity Infertility and nulliparity are associated with a higher incidence of breast cancer, as is a first pregnancy later than 35 years of age. Physical exercise has a protective effect.

Natural History The natural history of breast cancer is cited in studies from the late 1800s at London's Middlesex Hospital, where median survival for 250 untreated patients was 2.7 years; survival was calculated from the description of onset of the first symptoms. Five-year survival was 18 percent, and 10-year survival 3.76 percent. Autopsies showed that 95 percent of the women died of breast carcinoma, and 75 percent had breast ulceration at death.

Biology of Breast Cancer A typical scirrhous adenocarcinoma begins in the upper outer quadrant (45 percent) of the left breast (60 percent) and takes 30 doublings from the one-cell stage over 5–8 years to reach a palpable size (1 cm in diameter). Metastasis may begin when the tumor is greater than 0.5 cm in diameter, and prognosis is adversely affected by the increasing number of axillary lymph nodes involved. As the tumor progresses, fibrosis shortens Cooper's ligament with characteristic skin dimpling. Systemic spread is most common to bone (49–60 percent), lung (15–20 percent), and liver (5–15 percent). In general, 10–30 percent of recurrences are local, 60–70 percent are distant, and 10–30 percent are both (local and distant). Sixty percent of patients who develop metastatic disease do so within 24 months of the initial definitive treatment.

Staging of Breast Cancer

Staging provides an overall perspective of the disease as it relates to prognosis. It includes data on the status of potential sites of regional metastases (lymph nodes) and distant sites (lungs, bones, liver, etc.). Besides tumor size and lymph node metastases, the absolute number of lymph nodes involved is extremely significant. Node-negative status is associated with only 20 percent treatment failure in 10 years, as compared with 71 percent failure in patients with more than four positive nodes. Sentinel node biopsy following lymphatic mapping (with dye or radioisotope) as an alternative to axillary dissection is still under clinical investigation.

Bone scan, computed tomography (CT), and magnetic resonance imaging (MRI) as staging tools are used commonly, even though they have poor specificity.
Hormone receptors, flow cytometry, genetic information, c-erbB-2 oncogene evaluation, and other biologic parameters are profiled in clinical practice not only for prognostic and staging purposes but also for therapeutic planning.

Among the three staging systems available, the one modified by the American Joint Committee on Cancer (AJCC) based on TNM is followed (Table 14-2).

TABLE 14-2 MANUAL FOR STAGING OF CANCER*

Histopathology/Epidemiology

Carcinomas of ductal origin are most frequent and comprise about 80 percent of all breast cancers. The noninfiltrating (in situ) cancers do not invade beyond the investing basement membrane. The ductal or lobular in situ carcinoma (DCIS or LCIS), therefore, is unlikely to metastasize and carries a favorable prognosis. With progression, invasion beyond the basement membrane (as in infiltrating cancer) renders the lymphatics vulnerable, and thus nodal and distant metastases become a possibility. The original classification of breast malignancies proposed by Foote and Stevens is as follows:

Paget's disease
Carcinomas of ductal origin
1. Noninfiltrating (DCIS)
2. Infiltrating (scirrhous, medullary, colloid, papillary, etc.)
Carcinoma of mammary lobules
1. Noninfiltrating (LCIS)
2. Infiltrating (infiltrating lobular)
Rare carcinomas
Sarcomas

Noninfiltrating Malignancies

Ductal Carcinoma in Situ (DCIS) Increased use of mammography has enabled early detection of cancer and a considerable rise in its percentage as noninvasive type. In the earlier literature, the incidence of DCIS was 1.4 percent among all biopsies, but recent series show an increase to 7 percent of all breast biopsies and nearly 30 percent of the nonpalpable malignancies. Histologically, four different patterns were identified: cribriform, solid, micropapillary, and comedo. The newer classification suggests division into three categories: (1) noncomedo without necrosis, (2) noncomedo with necrosis, and (3) comedo. Comedo is considered to be the most biologically aggressive, with a higher incidence of multicentricity and recurrence.

Lobular Carcinoma in Situ (LCIS) Ninety percent of LCIS lesions occur in premenopausal women, and these lesions are 12 times more common in white women than in African-American women. There is a significant rate of bilaterality. Both DCIS and LCIS can be multicentric, the latter having a higher incidence than DCIS. Multifocality refers to occult malignancy in the same quadrant as the index lesion, whereas multicentricity refers to the presence of disease in a different quadrant. About 10–30 percent of LCIS patients will develop subsequent invasive carcinoma 15–20 years later.

Infiltrating Malignancies

Infiltrating Ductal Carcinoma This is the most common form of breast cancer (78 percent), typically characterized by productive fibrosis (scirrhous) changes. It is usually seen in the perimenopausal age group as a firm, poorly defined, painless mass. Further progression and infiltration by the tumor cause Cooper's ligaments to shorten, resulting in dimpling of the overlying skin. A generic term used for this type of tumor is invasive duct carcinoma not otherwise specified (NOS). More specific duct carcinomas are medullary, papillary, tubular, colloid, and others that show specific histologic features with possible differences in their progress.

Medullary Carcinomas Medullary carcinomas represent 2–15 percent of invasive cancers. They are usually large, bulky, and hemorrhagic. There is lymphocytic infiltrate accompanied by active mitosis. About 40 percent have axillary lymph node metastases.

Mucinous Carcinoma (Colloid Carcinoma) This ductal cancer constitutes about 2 percent of breast cancers. The tumor is bulky and gelatinous. Five-year survival is 73 percent.

Tubular Carcinoma Tubular carcinoma is easily diagnosed mammographically and generally in the perimenopausal age. It has excellent survival.

Papillary Carcinoma Papillary carcinoma is generally seen in older women (seventh decade) and more commonly in non-Caucasians. The tumor is well circumscribed and has a lower incidence of axillary nodal involvement. It has the best 5-and 10-year survival rates.

Inflammatory Carcinoma Inflammatory carcinoma represents a type of aggressive, rapidly advancing ductal carcinoma with clinical features of inflammation. Erythema, peau d'orange, and skin ridging generally are mistaken for infection. Usually it lacks elements of pain and fever. This carcinoma generally involves the dermal lymphatics, and about 75 percent of patients have palpable axillary metastases. Five-year survival is dismal.

Paget's Disease of the Nipple Paget's disease of the nipple generally presents as a chronic nonhealing eczematoid excoriation of the nipple. It is almost always associated with underlying intraductal or invasive carcinoma. Microscopically, the tumor consists of large, pale, vacuolated cells (Paget's cells). Prognosis is better than that for the average ductal carcinoma.

Infiltrating Lobular Carcinoma This carcinoma originates in terminal ductules of the lobule and has features different from ductal cancers. Infiltrating lobular carcinoma constitutes about 10 percent of breast cancers. It has a high incidence of bilaterality, multicentricity, and multifocality.

Sarcomas Sarcomas of the breast are generally heterogeneous. These include fibrosarcoma, liposarcoma, and leiomyosarcoma and present as large, painless breast masses. Some sarcomas are well circumscribed, whereas others have infiltrative, ill-defined margins.

Angiosarcoma Angiosarcoma develops generally in an irradiated upper extremity or chest wall. Prognosis is extremely poor, and 5-year survival is rare.

Treatment

Surgical Treatment Halsted in 1882 performed his first radical mastectomy—even though he did not report it until 1890–1891. This refined the concept originally advanced by Jean Louis Petit (1674–1750). It entailed removal of the breast, both pectoralis major and minor, and the axillary lymph nodes to establish local-regional control. Patient selection is considered important, and not all patients are suitable for curative surgical intervention. The criteria of inoperability include patients with near certainty of developing distant metastases—e.g., tumor fixity to chest wall, fixity of axillary nodes, inflammatory breast carcinoma, satellite nodules, supraclavicular nodes, and arm edema. Halsted's criteria excluded 25 percent of patients from surgical therapy. At present, about 10 percent of patients exhibit these criteria, and most of them (80 percent) are reverted successfully (“downstaged”) to operable status with chemotherapy and radiotherapy (neoadjuvant treatment).

Modifications of (Halsted's) radical mastectomy include preservation of the pectoralis major (Patey), preservation of both muscles (Madden), and extention of the Halsted mastectomy to include the internal mammary lymph nodes and adjacent chest wall (Urban).

Breast-conservation surgery implies limiting the amount of resected volume of breast tissue with the tumor and still trying to achieve as effective a local control as with mastectomy. Lumpectomy, segmental resection, and quadrantectomy (with or without axillary node dissection) in combination with radiation therapy are the options available. In 1980, Veronesi reported similar survival and recurrence rates in patients with tumors 2 cm in size or smaller with palpable axillary nodes whether they underwent radical mastectomy or quadrantectomy with axillary node dissection and radiation therapy (QU.A.R.T.). In 1985, the National Surgical Adjuvant Breast Project (NSABP) study was reported by Fisher. It compared modified radical mastectomy with segmental resection, axillary dissection, and radiation therapy in patients with tumors 4 cm in size or smaller. Survival and local recurrence rates were equal. In another group of patients in whom radiation was omitted, a high local recurrence rate was noted (24 percent in node-negative and 36 percent in node-positive patients). This clearly showed the benefit of radiation in breast conservation. Criteria for breast conservation generally include (1) small tumor size (<4 cm), (2) clinically negative axilla, (3) adequate breast volume, and (4) an experienced radiation therapist. It is important to achieve complete removal of cancer before the breast-conservation protocol is recommended.

PATIENT SELECTION

Multimodal therapy in the last 30 years has enhanced the local-regional control of advanced primary breast tumors. Surgical and radiation objectives are directed at local-regional pathology, while the medical oncologist aims to control systemic disease.

TREATMENT OF EARLY BREAST CANCER/IN SITU DISEASE

Ductal Carcinoma in Situ (DCIS) Even though total mastectomy offers almost 98 percent disease-free survival, less aggressive and limited resections and radiation in smaller tumors resulted in a 5-year recurrence rate of only 7.5 percent (NSABP, protocol 17). Combined data from 14 studies in 1098 women with DCIS treated with conservative surgery and radiation showed recurrence in 9.1 percent of patients—40 percent of these recurrent lesions were invasive. With controversial outcomes of conservative treatment, caution is warranted because safety and efficacy of limited surgery for DCIS are less certain. Postoperative radiation therapy is recommended, but the role of cytotoxic chemotherapy is questionable. Formal axillary node dissection is not warranted because the yield is less than 2 percent.

Lobular Carcinoma in Situ (LCIS) LCIS is a precursor of invasive cancer. Because the disease is usually diffuse and sometimes bilateral, local wide excision is not very beneficial. Since there is 5 percent risk of associated invasive cancer with multicentricity, operative therapy, e.g., total mastectomy, may be considered. Treatment of LCIS is still somewhat controversial.

TREATMENT OF STAGE I AND STAGE II BREAST CANCER

In the United States, partial mastectomy with radiation has gained popularity from 3.4 percent in 1972 to 25 percent in 1990. Modified radical mastectomy still is the most common procedure for breast cancer and more recently has been combined with immediate reconstruction. The recurrence rate at 5 years is similar in both groups, but 10-year disease-free survival is better with the more radical operation. Axillary dissection should be performed to adequately stage the disease. Mastectomy is preferred over segmental resection in patients with central (subareolar) lesions, extensive multicentric disease, large medial lesions (with potential for significant deformity after conservation), recurrent breast lesions who had been irradiated previously, or a contraindication to radiation (e.g., pulmonary or cutaneous pathology). In patients with extensive DCIS and some degree of invasion, there is 10 percent increased risk of recurrence when treated with local excision and radiation. In this subgroup, mastectomy is therefore preferable. Operative mortality with either treatment is less than 1 percent. Morbidity includes seroma, lymphedema, and some degree of sensory deficit in the axillary region.

Breast Reconstruction Immediate reconstruction at the time of mastectomy with autogenous tissue, e.g., a transverse rectus abdominis mycoutaneous (TRAM) flap or a latissimus dorsi flap, is becoming increasingly popular and is showing better success in achieving satisfactory cosmetic results. Use of a prosthesis should be deferred when chest wall irradiation is planned. A major drawback to reconstruction is delay in recognition of local recurrence.

Future Trends International trends favor less radical procedures and refining patient selection suitable for breast conservation without radiation and liberal use of systemic adjuvant therapy. The role of axillary lymph node dissection is under review, and limiting it to sentinel node biopsy may evolve as an acceptable procedure with less morbidity.

TREATMENT OF ADVANCED LOCAL DISEASE (STAGE III AND INFLAMMATORY CARCINOMA)

Combination chemotherapy (CAF—cyclophosphamide, Adriamycin, and 5-fluorouracil) induces regression of breast lesions. Following two to six drug cycles, an extended simple mastectomy can be performed. Subsequent to this, radiation therapy is used. This regimen yields about 30 percent 5-year survival.

TREATMENT OF RECURRENT AND METASTATIC DISEASE (STAGE IV)

Local recurrence may be treated by excision. Regional recurrence or localized osseous metastases may benefit from radiation therapy. Treatment is palliative. Metastatic disease generally is treated with polychemotherapy, indicating an improved response rate from 25 to 50–60 percent, and the median duration of response ranges from 12–18 months. Stage IV patients who achieve complete remission have a median survival of 32 months. Ablation (oophorectomy or adrenalectomy), additive therapy (high-dose estrogen or progesterone), antiestrogens (Tamoxifen), and antiadrenal agents (aminoglutethimide) have the same response (60 percent). Tamoxifen has the fewest side effects (hot flashes and mild cytopenia) and is the therapy of choice in patients with estrogen receptor (ER)–positive tumors.

ADJUVANT THERAPY

Node-Positive Breast Cancer The use of adjuvant therapy is predicated on the clinical data that cytotoxic therapy and hormonal therapy in patients with axillary metastases and no distant metastases prolong the disease-free interval and enhance survival rates. In patients with distant disease, polychemotherapy combinations of either cyclophosphamide (Cytoxan), methotrexate, and 5-fluorouracil (CMF) or that of cyclophosphamide, doxorubicin (Adriamycin), and 5-fluorouracil (CAF) are used most commonly. Prednisone or vincristine is sometimes added to the regimen. Variation in response is largely due to heterogeneity of the cell population of the tumor. Hormone receptors commonly studied are estrogen receptor (ER) and progesterone receptor (PR) proteins that bind and transfer steroid moiety into the cell nucleus. About 30 percent of premenopausal and 60 percent of postmenopausal women have ER-positive activity, and clinical response to antiestrogenic drugs correlates with the degree of ER/PR activity. Primary and metastatic tumors usually respond equally. Pre- and perimenopausal node-positive patients usually receive a 6-month course of CMF. Postmenopausal node-positive and ER-positive patients benefit from Tamoxifen, whereas ER-negative patients may receive chemotherapy (Table 14-3).

TABLE 14-3 PROPOSED THERAPEUTIC OPTIONS AND FREQUENCY OF STEROID RECEPTORS FOR PREMENOPAUSAL AND POSTMENOPAUSAL PATIENTS WITH BREAST CANCER

Node-Negative Breast Cancer Data suggest that (1) the majority of node-negative patients are cured by breast conservation or mastectomy and axillary node dissection and (2) recurrence is decreased by both chemotherapy and Tamoxifen. Poor response is usually expected in patients with lymphatic or vascular permeation, ER negativity, poor nuclear grade, high aneuploidy, and large tumor size.

Adjuvant radiation is used postoperatively in combination with breast-conserving surgery or in patients at high risk for local recurrence, e.g., chest wall fixity of tumor or with more than four positive nodes.

Prognosis

Stage I breast cancer 5-year survival approaches more than 85 percent, and for Stage II, the figure is 66 percent.
Stage III survival has improved with adjuvant therapy to about 40 percent.
Stage IV crude 5-year survival approaches about 10 percent.

NEWER TREATMENT MODALITIES

Trials of normal autologous bone marrow transplantation allowing high-dose chemotherapy has shown limited success. New biologic approaches targeted to inhibit angiogenesis (with angiostatin and endostatin) and growth factor receptor HER-2/neu (with herceptin) are being introduced at the present time with some promise. Recently introduced drugs, e.g., anastrozole (Arimidex), toremifene (Fareston), and Taxol, are being used more liberally as their clinical application becomes more defined.

Carcinoma of the Male Breast

About 1 percent of all breast cancer occurs in men. Incidence peaks between 60 and 69 years of age. Treatment is generally modified radical mastectomy. Adjuvant therapy is recommended for node-positive patients.

Breast Cancer during Pregnancy and Lactation

Incidence ranges from 0.4–3.8 percent of all reported breast cancers. The diagnosis is delayed because of difficulty in clinical examination and radiologic workup of the breast. Treatment is identical to that for nonpregnant patients. For Stage I and II disease, modified radical mastectomy is indicated. After mastectomy, normal pregnancy is allowed to continue. Chemotherapy, if indicated, is delayed until the second trimester. Breast conservation is generally to be discouraged except in the third trimester when radiation therapy can be delayed (for 2–6 weeks) until the delivery.

Rehabilitation

Once the wound is securely healed and the drainage tubes are removed, exercises are begun to restore the ipsilateral arm to full function and range of motion. Elevation and sequential compression help decrease the lymphedema. Support groups are available through the American Cancer Society and various hospital-sponsored breast centers to fulfill emotional and informational needs.

For a more detailed discussion, see Kirby I. Bland, Michael P. Vezeridis, and Edward M. Copeland III: Breast, chap. 14 in Principles of Surgery, 7th ed.