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Surgery_Schwartz. of their breast cancer (objective response) or long-term stabilization of disease (stable disease) are con-sidered to represent “clinical benefit” and should receive addi-tional endocrine therapy at the time of progression because their chances of a further response remain high.294-296 Patients whose tumors progress de novo on an endocrine agent have a low rate of clinical benefit (<20%) to subsequent endocrine therapy; the choice of endocrine or chemotherapy should be considered based on the disease site and extent as well as the patient’s general condition and treatment preference.294The adjuvant use of aromatase inhibitors and recent advances in tumor genome sequencing technologies have enabled the identification of secondary ESR1 mutations.347,348 These mutations, typically present in the ligand binding domains, lead to ligand-independent activation of the receptor, mediate resistance to aromatase inhibitors, and are associated with shorter survival.349 Reported incidence of these


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Surgery_Schwartz. the ligand binding domains, lead to ligand-independent activation of the receptor, mediate resistance to aromatase inhibitors, and are associated with shorter survival.349 Reported incidence of these mutations are variable (20%–30%) based on prior exposure to aroma-tase inhibitors and are uncommon in primary breast cancers. Clinical trials evaluating novel selective estrogen receptor degraders with potential activity against these mutations are in progress.Ablative Endocrine TherapyIn the past, adrenalectomy and/or hypophysectomy were the pri-mary endocrine modalities used to treat metastatic breast cancer, but today these approaches are seldom used. In women who are premenopausal at diagnosis, ovarian ablation can be accomplished by oophorectomy or ovarian radiation. Ovarian suppression can be accomplished by the use of gonadotrophin-hormone releasing hormone agonists, such as goserelin or leuprolide. Evaluation of the combination of goserelin with tamoxifen vs.


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Surgery_Schwartz. Ovarian suppression can be accomplished by the use of gonadotrophin-hormone releasing hormone agonists, such as goserelin or leuprolide. Evaluation of the combination of goserelin with tamoxifen vs. cyclophospha-mide/methotrexate/fluorouracil chemotherapy in premenopausal ER-positive early-stage breast cancers showed that relapse-free survival was superior with endocrine therapy combination, with a similar trend in overall survival.350 Data from the SOFT and TEXT trials on adjuvant endocrine therapy show that exemes-tane plus ovarian suppression significantly reduces recurrences as compared with tamoxifen plus ovarian suppression.351,352 In these trials, ovarian suppression was achieved with the use of the gonadotropin-releasing hormone agonist triptorelin, oopho-rectomy, or ovarian irradiation. The disease-free survival was 89% in the tamoxifen plus ovarian suppression group, while it was 93% in exemestane plus ovarian suppression group; how-ever, there was no significant


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Surgery_Schwartz. irradiation. The disease-free survival was 89% in the tamoxifen plus ovarian suppression group, while it was 93% in exemestane plus ovarian suppression group; how-ever, there was no significant differences in overall survival. In the SOFT trial, while tamoxifen plus ovarian suppression was not superior to tamoxifen alone in terms of disease-free survival, improved outcomes were observed in ovarian suppression in women with a high risk of recurrence. In women who received no adjuvant chemotherapy, no meaningful benefit was obtained with ovarian suppression. Thus, ovarian suppression in combi-nation with an aromatase inhibitor can be considered in select premenopausal women with high-risk features (age <40 years, positive lymph nodes) who warranted adjuvant chemotherapy.Anti-HER2 TherapyThe determination of tumor HER-2 expression or gene ampli-fication for all newly diagnosed patients with breast cancer is now recommended.353-356 It is used to assist in the selection of adjuvant


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Surgery_Schwartz. determination of tumor HER-2 expression or gene ampli-fication for all newly diagnosed patients with breast cancer is now recommended.353-356 It is used to assist in the selection of adjuvant chemotherapy in both node-negative and node-positive patients. Trastuzumab was initially approved for the treatment of HER2/neu-positive breast cancer in patients with metastatic disease. Once efficacy was demonstrated for patients with metastatic disease, the NSABP and the North Central Cancer Treatment Group conducted phase 3 trials that evaluated the impact of adjuvant trastuzumab therapy in patients with early-stage breast cancer. After approval from the FDA, these groups amended their adjuvant trastuzumab trials (B-31 and N9831, respectively), to provide for a joint efficacy analysis. The first joint interim efficacy analysis demonstrated an improvement in 3-year disease-free survival from 75% in the control arm to 87% in the trastuzumab arm (hazard ratio = 0.48, P <.0001). There was an


Surgery_Schwartz

Surgery_Schwartz. joint interim efficacy analysis demonstrated an improvement in 3-year disease-free survival from 75% in the control arm to 87% in the trastuzumab arm (hazard ratio = 0.48, P <.0001). There was an accompanying 33% reduction in mortality in the patients who received trastuzumab (hazard ratio = 0.67, P = 0.015). The magnitude of reduction in hazard for disease-free survival events crossed prespecified early reporting boundaries, so the data-monitoring committees for both groups recommended that randomized accrual to the trials be ended, and the results were subsequently published.181While anthracycline-based adjuvant chemotherapy was considered preferable in HER2-positive breast cancer, the BCIRG 006 compared the use of anthracycline with taxane and trastuzumab (AC-TH) versus taxane, carboplatin chemotherapy with trastuzumab (TCH).182 With 10 years of follow-up, no statistical significance with regard to disease-free and overall Brunicardi_Ch17_p0541-p0612.indd 59801/03/19 5:05 PM


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Surgery_Schwartz. chemotherapy with trastuzumab (TCH).182 With 10 years of follow-up, no statistical significance with regard to disease-free and overall Brunicardi_Ch17_p0541-p0612.indd 59801/03/19 5:05 PM 599THE BREASTCHAPTER 17survival was observed for anthracycline-based chemotherapy. While anthracycline chemotherapy was numerically superior, this was accompanied by an increase in the incidence of leu-kemia and congestive heart failure. A year of adjuvant trastu-zumab is considered standard of care. Two years of adjuvant trastuzumab has been shown to be more effective, although it is associated with more toxicity than 1 year of trastuzumab.357 On the other hand, the PHARE trial examined 6 months vs. stan-dard 12 months of trastuzumab. After 3.5 years of follow-up, the study failed to demonstrate that 6 months was noninferior com-pared to the standard therapy.358 Patients with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy. Because of overlapping cardiotoxicities,


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Surgery_Schwartz. that 6 months was noninferior com-pared to the standard therapy.358 Patients with HER2-positive tumors benefit if trastuzumab is added to taxane chemotherapy. Because of overlapping cardiotoxicities, trastuzumab is not usu-ally given concurrently with anthracyclines.Buzdar and colleagues reported the results of a random-ized neoadjuvant trial of trastuzumab in combination with sequential paclitaxel followed by FEC-75 (5-fluorouracil, epi-rubicin, cyclophosphamide) vs. the same chemotherapy regimen without trastuzumab in 42 women with early-stage operable breast cancer. The pathologic complete response rates in this trial increased from 25% to 66.7% when chemotherapy was given concurrently with trastuzumab.301 A subsequent report that included additional patients treated with concurrent chemo-therapy and trastuzumab further confirmed the high pathologic complete response rates and continued to show that cardiac function was preserved.302While novel agents have been approved for the


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Surgery_Schwartz. chemo-therapy and trastuzumab further confirmed the high pathologic complete response rates and continued to show that cardiac function was preserved.302While novel agents have been approved for the treatment of women with metastatic HER2-positive breast cancers, cur-rently trastuzumab is the only HER2-targeted agent approved for use in the adjuvant setting. Lapatinib is a dual tyrosine kinase inhibitor that targets both HER2 and EGFR. It was approved for use with capecitabine in patients with HER2-positive meta-static disease. Adjuvant lapatinib was shown to be inferior to trastuzumab, and the combination of lapatinib with trastuzumab did yield a significant improvement in disease-free survival compared to trastuzumab alone. Ado-trastuzumab emtansine (T-DM1) is approved for HER2-positive metastatic breast cancer patients who have previously received trastuzumab and a taxane either separately or in combination. T-DM1 is an antibody drug conjugate that incorporates the HER2 targeted


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Surgery_Schwartz. metastatic breast cancer patients who have previously received trastuzumab and a taxane either separately or in combination. T-DM1 is an antibody drug conjugate that incorporates the HER2 targeted activity of trastuzumab with the cytotoxic activity of DM1, a microtubule inhibitory agent leading to apoptosis.359Pertuzumab is a humanized monoclonal antibody that binds at a different epitope of the HER2 extracellular domain (subdomain II) and prevents dimerization of HER2 with other members of the family, primarily HER3. In the metastatic setting, it is approved in combination with trastuzumab and docetaxel for patients with metastatic HER2-positive breast cancer who have not received prior HER2-targeted therapy or chemotherapy for metastatic disease.360 In the neoadjuvant setting, pertuzumab is approved in combination with trastu-zumab and docetaxel in HER2-positive, early stage breast cancers that are greater than 2 cm or node-positive. However, this approval is based on improvement in


Surgery_Schwartz

Surgery_Schwartz. is approved in combination with trastu-zumab and docetaxel in HER2-positive, early stage breast cancers that are greater than 2 cm or node-positive. However, this approval is based on improvement in pathologic complete response rate, and not data based on improvement in event free or overall survival.361,362 In the NeoSphere trial, neoadjuvant use of pertuzumab with trastuzumab and docetaxel led to nearly a 17% increase in pathologic complete response in the breast (P = .0141).361 While in the TRYPHAENA study, pathologic complete responses ranging from 57% to 66% were observed with neoadjuvant pertuzumab and trastuzumab combination given with anthracycline-containing or nonanthracycline-containing chemotherapy.362 With the use of dual antibody therapy, cur-rently there is significant interest in identifying patients who can avoid chemotherapy and potentially be treated with HER2-targeted agents alone. The NeoSphere study showed 27% pathologic complete response in HER2-positive,


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Surgery_Schwartz. interest in identifying patients who can avoid chemotherapy and potentially be treated with HER2-targeted agents alone. The NeoSphere study showed 27% pathologic complete response in HER2-positive, ER-negative, breast cancer patients treated with pertuzumab and trastuzumab alone. Pertuzumab was recently FDA approved in combination with trastuzumab and chemotherapy in the adjuvant setting in HER2 amplified breast cancers with high risk of recurrence. Approval is based on APHINITY trial showing that the addition of pertuzumab improved invasive disease free survival (7.1%) compared to placebo (8.7%) (HR 0.82, 95% CI: 0.67, 1.00; p = 0.047). Overall survival data is not mature.The ExteNET study evaluated the use of neratinib, an irreversible inhibitor of EGFR, HER2, and HER4, in HER2-positive early stage patients who have completed adjuvant trastuzumab. A year of neratinib after completion of chemo-therapy and trastuzumab-based adjuvant therapy significantly improved 2-year disease-free


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Surgery_Schwartz. early stage patients who have completed adjuvant trastuzumab. A year of neratinib after completion of chemo-therapy and trastuzumab-based adjuvant therapy significantly improved 2-year disease-free survival, the primary endpoint.363 After two years, invasive disease free survival was 94.2% in patients treated with neratinib compared with 91.9% in those receiving placebo (HR 0.66; 95% CI: 0.49, 0.90, p = 0.008) leading to FDA approval for HER2 amplified breast cancers following a year of adjuvant trastuzumab.In addition to amplifications or copy number alterations, activating mutations or single nucleotide variants in HER2 have been described (2%).364 Typically observed in ER-positive breast cancers, a higher prevalence of HER2 mutations have been reported in invasive lobular carcinomas, particularly in the pleomorphic subtype.365 These mutations, usually exclusive with HER2 amplification, are observed in kinase or extracellular domains and predict for responses or resistance to


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Surgery_Schwartz. particularly in the pleomorphic subtype.365 These mutations, usually exclusive with HER2 amplification, are observed in kinase or extracellular domains and predict for responses or resistance to HER2-targeting agents.366,367 A phase 2 trial of neratinib in HER2-mutated meta-static breast cancers showed a clinical benefit rate of 36% with one complete response and one partial response in a heavily pre-treated population. A clinical trial evaluating the combination of neratinib with fulvestrant, in HER2-mutated, ER-positive breast cancers, is in progress.SPECIAL CLINICAL SITUATIONSNipple DischargeUnilateral Nipple Discharge. Nipple discharge is a finding that can be seen in a number of clinical situations. It may be suggestive of cancer if it is spontaneous, unilateral, localized to a single duct, present in women ≥40 years of age, bloody, or associated with a mass. A trigger point on the breast may be present so that pressure around the nipple-areolar complex induces discharge from a


Surgery_Schwartz

Surgery_Schwartz. duct, present in women ≥40 years of age, bloody, or associated with a mass. A trigger point on the breast may be present so that pressure around the nipple-areolar complex induces discharge from a single duct. In this circumstance, mammography and ultrasound are indicated for further evalu-ation. A ductogram also can be useful and is performed by can-nulating a single discharging duct with a small nylon catheter or needle and injecting 1.0 mL of water-soluble contrast solu-tion. Nipple discharge associated with a cancer may be clear, bloody, or serous. Testing for the presence of hemoglobin is helpful, but hemoglobin may also be detected when nipple dis-charge is secondary to an intraductal papilloma or duct ecta-sia. Definitive diagnosis depends on excisional biopsy of the offending duct and any associated mass lesion. A 3.0 lacrimal duct probe can be used to identify the duct that requires exci-sion. Another approach is to inject methylene blue dye within


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Surgery_Schwartz. of the offending duct and any associated mass lesion. A 3.0 lacrimal duct probe can be used to identify the duct that requires exci-sion. Another approach is to inject methylene blue dye within Brunicardi_Ch17_p0541-p0612.indd 59901/03/19 5:05 PM 600SPECIFIC CONSIDERATIONSPART IIthe duct after ductography. The nipple must be sealed with collodion or a similar material so that the blue dye does not discharge through the nipple but remains within the distended duct facilitating its localization. Localization with a wire or seed is performed when there is an associated mass that lies >2.0 to 3.0 cm from the nipple.Bilateral Nipple Discharge. Nipple discharge is suggestive of a benign condition if it is bilateral and multiductal in origin, occurs in women ≤39 years of age, or is milky or blue-green. Prolactin-secreting pituitary adenomas are responsible for bilat-eral nipple discharge in <2% of cases. If serum prolactin levels are repeatedly elevated, plain radiographs of the


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Surgery_Schwartz. or blue-green. Prolactin-secreting pituitary adenomas are responsible for bilat-eral nipple discharge in <2% of cases. If serum prolactin levels are repeatedly elevated, plain radiographs of the sellaturcica are indicated, and thin section CT scan is required. Optical nerve compression, visual field loss, and infertility are associated with large pituitary adenomas.Axillary Lymph Node Metastases in the Setting of an Unknown Primary CancerA woman who presents with an axillary lymph node metasta-sis that is consistent with a breast cancer metastasis has a 90% probability of harboring an occult breast cancer.303 However, axillary lymphadenopathy is the initial presenting sign in only 1% of breast cancer patients. Fine-needle aspiration biopsy or core-needle biopsy can be used to establish the diagnosis when an enlarged axillary lymph node is identified. When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin.


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Surgery_Schwartz. diagnosis when an enlarged axillary lymph node is identified. When metastatic cancer is found, immunohistochemical analysis may classify the cancer as epithelial, melanocytic, or lymphoid in origin. The presence of hormone receptors (estrogen or progesterone receptors) suggests metastasis from a breast cancer but is not diagnostic. The search for a primary cancer includes careful examination of the thyroid, breast, and pelvis, including the rectum. The breast should be examined with diagnostic mam-mography, ultrasonography, and MRI to evaluate for an occult primary lesion. Further radiologic and laboratory studies should include chest radiography and liver function studies. Additional imaging of the chest, abdomen, and skeleton may be indicated if the extent of nodal involvement is consistent with stage III breast cancer. Suspicious findings on mammography, ultra-sonography, or MRI necessitate breast biopsy. When a breast cancer is found, treatment consists of an axillary lymph node


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Surgery_Schwartz. with stage III breast cancer. Suspicious findings on mammography, ultra-sonography, or MRI necessitate breast biopsy. When a breast cancer is found, treatment consists of an axillary lymph node dissection with a mastectomy or preservation of the breast fol-lowed by whole-breast radiation therapy. Chemotherapy and endocrine therapy should be considered.Breast Cancer During PregnancyBreast cancer occurs in 1 of every 3000 pregnant women, and axillary lymph node metastases are present in up to 75% of these women.368 The average age of the pregnant woman with breast cancer is 34 years. Fewer than 25% of the breast nodules developing during pregnancy and lactation will be cancerous. Ultrasonography and needle biopsy specimens are used in the diagnosis of these nodules. Mammography is rarely indicated because of its decreased sensitivity during pregnancy and lac-tation; however, the fetus can be shielded if mammography is needed. Approximately 30% of the benign conditions encoun-tered will


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Surgery_Schwartz. because of its decreased sensitivity during pregnancy and lac-tation; however, the fetus can be shielded if mammography is needed. Approximately 30% of the benign conditions encoun-tered will be unique to pregnancy and lactation (galactoceles, lobular hyperplasia, lactating adenoma, and mastitis or abscess). Once a breast cancer is diagnosed, complete blood count, chest radiography (with shielding of the abdomen), and liver function studies are performed.Because of the potential deleterious effects of radiation therapy on the fetus, radiation cannot be considered until the fetus is delivered. A modified radical mastectomy can be per-formed during the first and second trimesters of pregnancy, even though there is an increased risk of spontaneous abortion after first-trimester anesthesia. During the third trimester, lumpec-tomy with axillary node dissection can be considered if adju-vant radiation therapy is deferred until after delivery. Lactation is suppressed. Chemotherapy


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Surgery_Schwartz. During the third trimester, lumpec-tomy with axillary node dissection can be considered if adju-vant radiation therapy is deferred until after delivery. Lactation is suppressed. Chemotherapy administered during the first tri-mester carries a risk of spontaneous abortion and a 12% risk of birth defects. There is no evidence of teratogenicity resulting from administration of chemotherapeutic agents in the second and third trimesters. For this reason, many clinicians now con-sider the optimal strategy to be delivery of chemotherapy in the second and third trimesters as a neoadjuvant approach, which allows local therapy decisions to be made after the delivery of the baby. Pregnant women with breast cancer often present at a later stage of disease because breast tissue changes that occur in the hormone-rich environment of pregnancy obscure early cancers. However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast


Surgery_Schwartz

Surgery_Schwartz. the hormone-rich environment of pregnancy obscure early cancers. However, pregnant women with breast cancer have a prognosis, stage by stage, that is similar to that of nonpregnant women with breast cancer.Male Breast CancerFewer than 1% of all breast cancers occur in men.369,370 The inci-dence appears to be highest among North Americans and the British, in whom breast cancer constitutes as much as 1.5% of all male cancers. Jewish and African-American men have the highest incidence. Male breast cancer is preceded by gyneco-mastia in 20% of men. It is associated with radiation exposure, estrogen therapy, testicular feminizing syndromes, and Kline-felter’s syndrome (XXY). Breast cancer is rarely seen in young males and has a peak incidence in the sixth decade of life. A firm, nontender mass in the male breast requires investigation. Skin or chest wall fixation is particularly worrisome.DCIS makes up <15% of male breast cancer, whereas infil-trating ductal carcinoma makes up >85%.


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Surgery_Schwartz. mass in the male breast requires investigation. Skin or chest wall fixation is particularly worrisome.DCIS makes up <15% of male breast cancer, whereas infil-trating ductal carcinoma makes up >85%. Special-type cancers, including infiltrating lobular carcinoma, have occasionally been reported. Male breast cancer is staged in the same way as female breast cancer, and stage by stage, men with breast cancer have the same survival rate as women. Overall, men do worse because of the more advanced stage of their cancer (stage II, III or IV) at the time of diagnosis. The treatment of male breast cancer is surgi-cal, with the most common procedure being a modified radical mastectomy. SLN dissection has been shown to be feasible and accurate for nodal assessment in men presenting with a clinically node-negative axilla. Adjuvant radiation therapy is appropriate in cases in which there is a high risk for local-regional recurrence. Approximately 80% of male breast cancers are hormone


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Surgery_Schwartz. a clinically node-negative axilla. Adjuvant radiation therapy is appropriate in cases in which there is a high risk for local-regional recurrence. Approximately 80% of male breast cancers are hormone recep-tor–positive, and adjuvant tamoxifen is considered. Systemic che-motherapy is considered for men with hormone receptor-negative cancers and for men with large primary tumors, multiple positive nodes, and locally advanced disease.Phyllodes TumorsThe nomenclature, presentation, and diagnosis of phyllodes tumors (including cystosarcoma phyllodes) have posed many problems for surgeons.371 These tumors are classified as benign, borderline, or malignant. Borderline tumors have a greater potential for local recurrence.Mammographic evidence of calcifications and morpho-logic evidence of necrosis do not distinguish between benign, borderline, and malignant phyllodes tumors. Consequently, it is difficult to differentiate benign phyllodes tumors from the Brunicardi_Ch17_p0541-p0612.indd


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Surgery_Schwartz. do not distinguish between benign, borderline, and malignant phyllodes tumors. Consequently, it is difficult to differentiate benign phyllodes tumors from the Brunicardi_Ch17_p0541-p0612.indd 60001/03/19 5:05 PM 601THE BREASTCHAPTER 17malignant variant and from fibroadenomas. Phyllodes tumors are usually sharply demarcated from the surrounding breast tissue, which is compressed and distorted. Connective tissue composes the bulk of these tumors, which have mixed gelati-nous, solid, and cystic areas. Cystic areas represent sites of infarction and necrosis. These gross alterations give the gross cut tumor surface its classical leaf-like (phyllodes) appearance. The stroma of a phyllodes tumor generally has greater cellular activity than that of a fibroadenoma. After microdissection to harvest clusters of stromal cells from fibroadenomas and from phyllodes tumors, molecular biology techniques have shown the stromal cells of fibroadenomas to be either polyclonal or mono-clonal (derived


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Surgery_Schwartz. clusters of stromal cells from fibroadenomas and from phyllodes tumors, molecular biology techniques have shown the stromal cells of fibroadenomas to be either polyclonal or mono-clonal (derived from a single progenitor cell), whereas those of phyllodes tumors are always monoclonal.Most malignant phyllodes tumors (Fig. 17-38) contain liposarcomatous or rhabdomyosarcomatous elements rather than fibrosarcomatous elements. Evaluation of the number of mitoses and the presence or absence of invasive foci at the tumor mar-gins may help to identify a malignant tumor. Small phyllodes tumors are excised with a margin of normal-appearing breast tissue. When the diagnosis of a phyllodes tumor with suspicious ABFigure 17-38. A. Malignant phyllodes tumor (cystosarcoma-phyllodes). B. Histologic features of a malignant phyllodes tumor (hematoxylin and eosin stain, ×100).malignant elements is made, reexcision of the biopsy specimen site to ensure complete excision of the tumor with a 1-cm mar-gin of


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Surgery_Schwartz. of a malignant phyllodes tumor (hematoxylin and eosin stain, ×100).malignant elements is made, reexcision of the biopsy specimen site to ensure complete excision of the tumor with a 1-cm mar-gin of normal-appearing breast tissue is indicated. Large phyl-lodes tumors may require mastectomy. Axillary dissection is not recommended because axillary lymph node metastases rarely occur.Inflammatory Breast CarcinomaInflammatory breast carcinoma (stage IIIB) accounts for <3% of breast cancers. This cancer is characterized by the skin changes of brawny induration, erythema with a raised edge, and edema (peau d’orange).372 Permeation of the dermal lymph vessels by cancer cells is seen in skin biopsy specimens. There may be an associated breast mass (Fig. 17-39). The clinical differentia-tion of inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d’orange and lymphangitis (Table


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Surgery_Schwartz. inflammatory breast cancer may be extremely difficult, especially when a locally advanced scirrhous carcinoma invades dermal lymph vessels in the skin to produce peau d’orange and lymphangitis (Table 17-15). Inflammatory breast cancer also may be mistaken for a bacterial infection of the breast. More than 75% of women who have inflammatory breast cancer present with palpable axillary lymphadenopathy, and distant metastases also are frequently present. A PET-CT scan should be considered at the time of diagnosis to rule out concurrent metastatic disease. A report of the SEER program described distant metastases at diagnosis in 25% of white women with inflammatory breast carcinoma.Surgery alone and surgery with adjuvant radiation therapy have produced disappointing results in women with inflamma-tory breast cancer. However, neoadjuvant chemotherapy with an anthracycline-containing regimen may affect dramatic regres-sions in up to 75% of cases. Tumors should be assessed for HER2 and


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Surgery_Schwartz. inflamma-tory breast cancer. However, neoadjuvant chemotherapy with an anthracycline-containing regimen may affect dramatic regres-sions in up to 75% of cases. Tumors should be assessed for HER2 and hormone receptors with treatment dictated based on receptor status. Modified radical mastectomy is performed after demonstrated response to systemic therapy to remove residual cancer from the chest wall and axilla. Adjuvant chemotherapy may be indicated depending on final pathologic assessment of the breast and regional nodes. Finally, the chest wall and the Figure 17-39. Inflammatory breast carcinoma. Stage IIIB cancer of the breast with erythema, skin edema (peau d’orange), nipple retraction, and satellite skin nodules.Brunicardi_Ch17_p0541-p0612.indd 60101/03/19 5:06 PM 602SPECIFIC CONSIDERATIONSPART IIsupraclavicular, internal mammary, and axillary lymph node basins receive adjuvant radiation therapy. This multimodal approach results in 5-year survival rates that approach 30%.


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Surgery_Schwartz. CONSIDERATIONSPART IIsupraclavicular, internal mammary, and axillary lymph node basins receive adjuvant radiation therapy. This multimodal approach results in 5-year survival rates that approach 30%. Patients with inflammatory breast cancer should be encouraged to participate in clinical trials.Rare Breast CancersSquamous Cell (Epidermoid) Carcinoma. Squamous cell (epidermoid) carcinoma is a rare cancer that arises from metaplasia within the duct system and generally is devoid of distinctive clinical or radiographic characteristics.373 Regional metastases occur in 25% of patients, whereas distant metastases are rare.Adenoid Cystic Carcinoma. Adenoid cystic carcinoma is very rare, accounting for <0.1% of all breast cancers. It is typically indistinguishable from adenoid cystic carcinoma arising in sali-vary tissues. These cancers are generally 1 to 3 cm in diameter at presentation and are well circumscribed. Axillary lymph node metastases are rare, but deaths from pulmonary metastases


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Surgery_Schwartz. in sali-vary tissues. These cancers are generally 1 to 3 cm in diameter at presentation and are well circumscribed. Axillary lymph node metastases are rare, but deaths from pulmonary metastases have been reported.Apocrine Carcinomas. Apocrine carcinomas are well-differentiated cancers that have rounded vesicular nuclei and prominent nucleoli. There is a very low mitotic rate and little variation in cellular features. However, apocrine carcinomas may display an aggressive growth pattern.Sarcomas. Sarcomas of the breast are histologically similar to soft tissue sarcomas at other anatomic sites. This diverse group includes fibrosarcoma, malignant fibrous histiocytoma, liposarcoma, leiomyosarcoma, malignant schwannoma, rhab-domyosarcoma, osteogenic sarcoma, and chondrosarcoma. The clinical presentation is typically that of a large, painless breast mass with rapid growth. Diagnosis is by core-needle biopsy or by open incisional biopsy. Sarcomas are graded based on cellular-ity, degree of


Surgery_Schwartz

Surgery_Schwartz. is typically that of a large, painless breast mass with rapid growth. Diagnosis is by core-needle biopsy or by open incisional biopsy. Sarcomas are graded based on cellular-ity, degree of differentiation, nuclear atypia, and mitotic activity. Primary treatment is wide local excision, which may necessitate mastectomy. Axillary dissection is not indicated unless there is biopsy proven lymph node involvement. Angiosarcomas are classified as de novo, as postradiation, or as arising in associa-tion with postmastectomy lymphedema. In 1948, Stewart and Treves described lymphangiosarcoma of the upper extremity in women with ipsilateral lymphedema after radical mastectomy.374 Angiosarcoma is now the preferred name. The average interval between modified radical or radical mastectomy and the devel-opment of an angiosarcoma is 7 to 10 years. Sixty percent of women developing this cancer have a history of adjuvant radia-tion therapy. Forequarter amputation may be necessary to palli-ate the


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Surgery_Schwartz. devel-opment of an angiosarcoma is 7 to 10 years. Sixty percent of women developing this cancer have a history of adjuvant radia-tion therapy. Forequarter amputation may be necessary to palli-ate the ulcerative complications and advanced lymphedema.Lymphomas. Primary lymphomas of the breast are rare, and there are two distinct clinicopathologic variants. One type occurs in women ≤39 years of age, is frequently bilateral, and has the histologic features of Burkitt’s lymphoma. The second type is seen in women ≥40 years of age and is usually of the B-cell type. Breast involvement by Hodgkin’s lymphoma has been reported. An occult breast lymphoma may be diagnosed after detection of palpable axillary lymphadenopathy. Treatment depends on the stage of disease. Lumpectomy or mastectomy may be required. Axillary dissection for clearance of disease may be necessary. Recurrent or progressive local-regional disease is best man-aged by chemotherapy and radiation therapy. The prognosis is


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Surgery_Schwartz. be required. Axillary dissection for clearance of disease may be necessary. Recurrent or progressive local-regional disease is best man-aged by chemotherapy and radiation therapy. The prognosis is favorable, with 5and 10-year survival rates of 74% and 51%, respectively. More recently anaplastic large cell lymphoma has been described in association with breast implants for cosmetic or reconstructive purposes. This disease is treated with complete excision of the implant capsule with any associated soft tissue mass. More advanced cases may require systemic therapy and radiation treatment.REFERENCESEntries highlighted in bright blue are key references. 1. Breasted JH. The Edwin Smith Surgical Papyrus. University of Chicago Press, 1930;405. 2. Celsus AC. De Medicina (ed Loeb Classical Library Ed). Cambridge: Harvard University Press; 1935;131. 3. Beenken SW. History of the therapy of breast cancer. In: Copeland BA, ed. The Breast: Comprehensive Manage-ment of Benign and Malignant


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Surgery_Schwartz. Library Ed). Cambridge: Harvard University Press; 1935;131. 3. Beenken SW. History of the therapy of breast cancer. In: Copeland BA, ed. The Breast: Comprehensive Manage-ment of Benign and Malignant Disorder. Philadelphia: Saunders;2004;5. 4. Le Dran F. Mémoire avec une précis de plusieurs observa-tions sur le. Mem Acad Roy Chir Paris. 1757;3:1. 5. Moore C. On the influence of inadequate operations on the theory of cancer. R Med Chir Soc. 1867;1:244. 6. Halsted WS I. The results of operations for the cure of cancer of the breast performed at the Johns Hopkins Hospital from June, 1889, to January, 1894. Ann Surg. 1894;20:497-555. 7. Haagensen CD, Stout AP. Carcinoma of the breast. II-criteria of operability. Ann Surg. 1943;118:1032-1051. 8. Patey DH, Dyson WH. The prognosis of carcinoma of the breast in relation to the type of operation performed. Br J Cancer. 1948;2:7-13. 9. Fisher B, Jeong JH, Anderson S, et al. Twenty-five-year follow-up of a randomized trial comparing radical


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Surgery_Schwartz. changes are present without dermal lymph vessel invasion.Cancer is not sharply delineated.Cancer is better delineated.Erythema and edema frequently involve >33% of the skin over the breast.Erythema is usually confined to the lesion, and edema is less extensive.Lymph node involvement is present in >75% of cases.Lymph nodes are involved in approximately 50% of the cases.Distant metastases are more common at the initial presentation (25% of cases).Distant metastases are less common at presentation. Modified with permission from Bland KI, Copeland ED: The Breast: Comprehensive Management of Benign and Malignant Diseases, 2nd ed. Philadelphia, PA: Elsesvier/Saunders; 1998.Brunicardi_Ch17_p0541-p0612.indd 60201/03/19 5:06 PM 603THE BREASTCHAPTER 17 12. Clarke M, Collins R, Darby S, et al. Effects of radiotherapy and of differences in the extent of surgery for early breast cancer on local recurrence and 15-year survival: an overview of the randomised trials. Lancet.


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