Management of non metastatic phyllodes tumors of the breast: review of the literature

Phyllodes tumors of the breast are rare tumors, accounting for less than 0.5% of all breast tumors. These tumors are comprised of both stromal and epithelial elements; and traditionally they are graded by the use of a set of histologic features into benign, borderline, and malignant subtypes. Unfortunately, the histologic classification of phyllodes tumors does not reliably predict clinical behavior.The mainstay of treatment of non metastatic phyllodes tumors of the breast is complete surgical resection with wide resection margins. Lumpectomy or partial mastectomy is the preferred surgical therapy. However, despite the complete surgical resection, local failure rate may be high; and 22% of malignant tumors may give rise to haematogenous metastases. The most frequent site of distant metastases is the lungs. Several predictive factors of recurrence and metastases have been described in the literature, such as positive surgical margins, increased stromal cellularity, stromal overgrowth, stromal atypia and increased mitotic activity.Nevertheless, the role of adjuvant therapies (radiotherapy and chemotherapy) is presently undefined and should be tested in multicenter, prospective, randomized trials.     

乳腺叶状肿瘤和巨纤维腺瘤的临床病理特征——附89例临床分析

 目的　探讨乳腺叶状囊肉瘤和巨纤维腺瘤的诊断和治疗。方法　回顾分析我院 1979～ 2 0 0 2年间外科收治的 89例乳腺叶状囊肉瘤和巨纤维腺瘤的临床特点 ,病理诊断和治疗方式。结果　 2 7例乳腺叶状囊肉瘤 ,行乳腺改良根治术 4例 ,乳腺单纯切除术 16例 ,肿瘤局部切除术 4例 ,肿瘤复发行扩大切除 3例 ,复发率 33.3% (9/ 2 7) ;6 2例乳腺巨纤维腺瘤行肿瘤局部切除术 4 0例 ,乳房单纯切除术 18例 ,改良根治术 4例 ,复发率 11.3% (7/ 6 2 )。结论　按照WHO乳腺肿瘤分类的标准 ,使用乳腺叶状肿瘤的统一名称 ,并与乳腺巨纤维瘤相鉴别 ,根据肿瘤分类采用不同的手术方法。     

Role of radiotherapy in sarcoma of the breast--a retrospective review of the M.D. Anderson experience.

BACKGROUND: The role of adjuvant radiotherapy for sarcoma of the breast, based on local extension of disease and patterns of failure, remains undefined because of the rarity of the disease presentation. METHODS: Fifty-nine cases of soft tissue sarcoma of the breast were retrospectively reviewed. Cystosarcoma phylloides was excluded from analysis. Surgical intervention consisted of segmental resection (n = 16) or mastectomy (n = 38); five patients underwent excisional biopsy. Adjuvant radiotherapy was administered in four patients following segmental resection and in 13 patients after mastectomy. Doses totaled 50 Gy in the majority of patients, and conventional criteria and radiotherapy techniques for adjuvant breast irradiation were used. RESULTS: None of the dissected axillary nodes contained metastatic tumor on pathologic review. Patterns of failure were evaluated. Tumor size (P < 0.03) and surgical margins (P < 0.002) were predictive of local failure (LF). Due to limited patient numbers, no statistical significance was identified with any treatment modality. Following mastectomy alone, LF occurred in 13 patients (34%) versus the 13% rate of LF with mastectomy and radiotherapy (P = NS). Distant metastases developed concurrently with the two local failures in the group that underwent mastectomy and radiation. After segmental mastectomy, LF occurred in 3 cases (25%) concurrent with distant metastases: no LF were noted after segmental mastectomy and radiation (P = 0.27). For all treatment groups, local recurrences were characterized as multiple and involved the chest wall. Local failure occurred in 60% of patients with positive surgical margins who did not receive adjuvant irradiation. Irrespective of surgical margins, over 75% of local recurrences developed among patients treated by surgery alone. CONCLUSIONS: The role of radiotherapy for breast sarcoma remains undefined due to the rarity of this disease presentation. This retrospective review failed to demonstrate a statistical benefit for the administration of adjuvant irradiation in sarcoma of the breast, probably because of limited patient numbers. Because large tumor size and positive surgical margins incur a higher risk for LF, radiotherapy is probably indicated in these cases. Axillary dissection obligates the radiotherapist to treat the axilla in order to include all tissues in the surgical bed, and should be avoided to reduce potential treatment related morbidity. Established therapeutic principles and techniques used for both soft tissue sarcoma and breast cancer should continue to be applied.     

Primary sarcoma of the breast

BACKGROUND AND OBJECTIVES: Primary sarcoma occurring in breast is rare and comprises 0.5-1% of all breast neoplasm. Majority of the series include both stromal and cystosarcoma phyllodes, only a few hundred cases of sarcomas other then cystosarcoma are reported. PATIENTS AND METHODS: We carried out a retrospective analysis of 19 patients with primary sarcoma of the breast treated between 1982 and 2002. RESULTS: Mean age of the patients was 38.6 years (12-70 years). Gradually progressive swelling was the commonest presenting feature. There were eight cases of angiosarcoma, four cases of spindle cell sarcoma, two each of pleomorphic sarcoma and stromal sarcoma, and one each of malignant fibrous histiocytoma, embryonal rhabdomyosarcoma, and sarcoma (NOS). Eight of these were high-grade (42%). Eight patients underwent either radical or modified mastectomy, three underwent wide excisions, and one underwent quadrantectomy. Ten (52.6%) patients received postoperative adjuvant radiation. Two patients received chemotherapy. After a mean follow-up time of 34.5 months (median 25 months), eight patients failed. Failure was local in five, opposite breast in one, and both local and distant in two. The disease free survival at 3-year was 39%. In univariate analysis only the margin of first surgery was found to be a significant predictor of survival (P = 0.05). CONCLUSIONS: Primary sarcomas of the breast are aggressive tumors. Surgical treatment should consist of at least simple mastectomy. All attempts should be made to achieve a negative margin as this appears to be the only factor influencing survival in these patients.     

Ten-year results of breast-conserving surgery and definitive irradiation for intraductal carcinoma (ductal carcinoma in situ) of the breast.

An analysis of 259 women with 261 treated breasts from nine institutions in Europe and the United States was performed to determine the 10-year results of the treatment of intraductal carcinoma of the breast with definitive irradiation. All patients had undergone complete gross excision of the primary intraductal carcinoma, and definitive breast irradiation was delivered in all cases. The median follow-up time was 78 months (range, 11 to 197 months). The 10-year actuarial overall survival rate was 94%, and the 10-year actuarial cause-specific survival rate (including deaths only from carcinoma of the breast) was 97%. The 10-year actuarial rate of freedom from distant metastases was 96%. There were 28 failures in the breast, and the 10-year actuarial rate of local failure was 16%. The pathologic type of local recurrences showed invasive ductal carcinoma in 14 of 28 recurrences (50%) and noninvasive ductal carcinoma in 14 of 28 recurrences (50%). The median time to local failure was 50 months (range, 17 to 129 months). Twenty-four of 28 patients with local failure were salvaged with additional treatment, generally mastectomy, and 4 of 28 patients with local failure subsequently had distant metastases. Median follow-up time after salvage treatment of breast recurrence was 29 months (range, 3 to 90 months). Two patients without local failure subsequently had distant metastases, one of which occurred after a node-positive, contralateral breast carcinoma. These results demonstrate high rates of overall survival, cause-specific survival, and freedom from distant metastases for the treatment of patients with intraductal carcinoma of the breast. The local recurrences within the treated breast were generally salvaged with additional treatment, although with limited follow-up. Because of the long natural history of intraductal carcinoma of the breast, prolonged and careful follow-up of patients after breast-conservation and definitive irradiation is required.     

The use of radiotherapy for treatment of isolated locoregional recurrence of breast carcinoma after mastectomy

The role of radiotherapy in the treatment of isolated local recurrence of breast cancer after mastectomy is controversial. In an attempt to define this role, the results of moderate-dose radiotherapy in 90 such patients were reviewed. The median follow-up time for these patients was 81 months. The actuarial probability of local control after treatment was 42% at 5 years and 35% at 10 years. Freedom from distant failure was 30% at 5 years and only 7% at 10 years. The rate of appearance of distant metastasis was fairly constant at approximately 20% of patients per year. Overall survival was 50% at 5 years and 26% at 10 years. Overall survival and relapse-free survival were both chiefly influenced by the disease-free interval (DFI). Patients who presented with a DFI of greater than or equal to 2 years had a 5-year actuarial overall survival rate of 58% compared to 33% for patients with a DFI of less than 2 years (P = 0.04). Subsequent local failures after radiotherapy were principally seen at the initial site of recurrence, but also at other sites in or at the edge of the radiation fields. These results strongly suggest that patients with apparently isolated local recurrence after mastectomy are incurable by further local treatment. Effective systemic therapy is required to improve the results in these patients. Radiotherapy is a useful palliative procedure in patients with long disease-free intervals. The role of radiotherapy in conjunction with systemic therapy is, as yet, undefined.     

Long-term results of surgical therapy for phyllodes tumor of the breast

We report that the long-term results of surgical therapy for phyllodes tumor of the breast. During ten years, we experienced twenty-eight patients of phyllodes tumors of the breast. They were treated by surgical operation. Twenty-one cases were performed local excision with at least 1 cm surgical margin, and seven cases were performed muscle preserving mastectomy without axillary lymph nodes dissection. Pathological surgical margins of all patients were negative. Five patients were recognized the local recurrence, and only one patient was recognized a distant metastasis. The total recurrence rate was 21.4%. The patients with local recurrence were diagnosed the benign phyllodes tumor of the breast at the first operation. The mean time to recurrence was 5.4 years. If the pathological diagnosis was benign phyllodes tumor and surgical margin was negative at the first operation, it is necessary to follow up the patients, because there is a risk of local and distant metastasis.     

The clinical and histologic criteria that predict metastases from cystosarcoma phyllodes.

A retrospective study of 33 patients with cystosarcoma phyllodes was done. Eight of these patients had metastases, and the clinical and histologic criteria predicting the development of metastases were examined. The most reliable predictor was the presence of stromal overgrowth; this appears to be necessary for metastasis to occur. Other useful indicators of clinical behavior were the degree of mitotic activity, nuclear pleomorphism, and infiltrating margins. Based on these data and a literature review, the authors suggest close follow-up of patients whose primary tumors contain areas of stromal overgrowth because, in all series combined, the risk of metastatic spread in such patients was 72% within 5 years. Among these high-risk patients, local recurrence is another indication that metastasis is likely.     

Comparison of conservative surgery and radiotherapy with mastectomy in the treatment of early breast cancer

We have compared overall survival, and local and distant recurrence-free survival in patients with early breast cancer treated by mastectomy, with patients treated by wide local excision and radiotherapy. To do this, we reviewed a consecutive, unselected series of patients presenting with early breast cancer (T0-T2, N0-N1b, UICC) between 1973 and 1981 to one surgeon (J.-C.G.) and one radiotherapist (H.T.F.). The mean follow-up was 9 years (minimum 6 years, maximum 14 years). Only 9 patients received any adjuvant therapy. At 10 years the relapse-free survival was 65% for both groups of patients; the overall 10-year survival was 70% for patients treated by wide local excision and radiotherapy, and 67% for patients treated by mastectomy. The actuarial loco-regional recurrence rate at 10 years was 15% for patients treated by wide local excision and 13% for patients treated by mastectomy. There were no significant differences in overall survival, loco-regional and distant relapse-free survival between the two groups of patients. Our results support other reports that conservative surgery and radiotherapy in early breast cancer does not adversely affect long-term prognosis.     

Cystosarcoma phyllodes. Diagnosis and management

The diagnosis and management of cystosarcoma phyllodes is analyzed by reviewing the literature and presenting cases from our institution. This rare neoplasm of the female breast represents less than 1% of all breast tumors. Most patients present in the fourth and fifth decades of life. The predominant complaint is a palpable mass in the breast. Systemic manifestations occur after metastases have developed. Treatment is surgical excision. There is some controversy, however, over which type of surgical procedure should be performed. We recommend total mastectomy. Local recurrence and metastases do occur and have been related to inadequate surgery and various histological characteristics (mitotic activity, tumor margin, and stromal cellular atypia).     

乳腺叶状囊肉瘤的诊断与治疗

1961年~1991年我院共收治乳腺叶状囊肉瘤共120例,全部均行手术治疗。局部切除术71例的术后复发率为48.3%(34/71),其中低度恶性66例的复发率为43.9%(29/66)。中度恶性5例全部复发。全乳切除术58例中术后仅1例高度恶性,复发。高度恶性13例(全乳切除6例,根治术7例)术后局部复发1例,远处转移6例(肺、胸膜转移各2例,肝转移1例,骨及脑转移各1例)。本文就其诊断及治疗进行分析和探讨。     

An analysis of 78 breast sarcoma patients without distant metastases at presentation

PURPOSE: A retrospective review of a single cancer center experience was undertaken to identify clinical or treatment prognostic factors for these unusual tumors, to allow for a recommendation regarding management. METHODS AND MATERIALS: The charts of 76 women and 2 men with breast sarcoma and without distant metastases at presentation registered from 1958 to 1990 were reviewed. Pathology was centrally reviewed in 54 cases. Histology, tumor size, grade, nodal status, age, menopausal status, history of benign breast disease, extent of surgery, resection margins, and radiation dose were each examined as potential prognostic factors by univariate analysis. To allow an analysis of radiation dose, total dose was normalized to a daily fraction size of 2 Gy. RESULTS: The median age at diagnosis was 50.5 years (13-82 years). The pathologic diagnosis was found to be malignant cystosarcoma phyllodes in 32 patients, with the remainder being stromal sarcoma (14), angiosarcoma (8), fibrosarcoma (7), carcinosarcoma (5), liposarcoma (4), other (8). Eighteen patients had grade I or II tumors, 43 had grade III or IV, and 18 were not evaluable. The 5- and 10-year actuarial rates for all 78 patients were 57% and 48% for cause-specific survival (CSS), and 47% and 42% for the relapse-free rates (RFR), respectively. The local relapse-free rate (LRFR) was 75% at both 5 and 10 years. The 5-year CSS for grade I or II tumors was 84% versus 55% for grade III or IV tumors (p = 0.01). Conservative surgery versus mastectomy did not lead to statistically significant different outcomes for CSS, RFR, or LRFR. The comparison of positive versus negative margins showed a 5-year LRFR of 33% versus 80% (p = 0.009). Pairwise comparisons of the 5-year CSS of 91% for > 48 Gy versus either 50% for < or = 48 Gy or 50% for no radiation showed p-values of 0.03 and 0.06, respectively. CONCLUSION: The authors propose that if negative surgical margins can be achieved, breast sarcoma should be managed by conservative surgery with postoperative irradiation to a microscopic tumoricidal dose (50 Gy) to the whole beast, and at least 60 Gy to the tumor bed. The decision to treat should be preceded by a preoperative multidisciplinary assessment. It is also recommended that an axillary lymph node dissection is not indicated, with the possible exception of patients with carcinosarcoma.     

乳腺叶状肿瘤的诊断及治疗

目的探讨乳腺叶状肿瘤的诊断和治疗.方法对经手术和病理诊断的48例乳腺叶状肿瘤的临床病理资料进行回顾性分析.结果48例中平均年龄为43.2岁.根据肿瘤生长方式,瘤细胞异型,核分裂和肿瘤坏死进行乳腺叶状肿瘤分级,良性26例,交界性12例,恶性10例.全部病例采用手术治疗,肿瘤单纯切除术23例,良性、交界性、恶性复发分别为3/18、2/3、2/2;肿瘤扩大切除术15例,良性、交界性、恶性复发分别为0/8、1/5、1/2;乳房切除术10例,交界性、恶性复发转移分别为0/4、2/6.结论乳腺叶状肿瘤可分良性、交界性和恶性三种类别,确诊和分级主要依靠病理组织检查.提示首次肿瘤彻底切除是治疗的关键,应根据组织分级及肿瘤大小决定手术方式.     

Cystosarcoma phyllodes of the breast: a case report in a 12-year-old girl

Breast tumors in adolescents are very rare and mostly benign. Fibroadenomas are the most frequent, but within the extensive differential diagnosis, the phyllodes tumor must be mentioned, which accounts for about 1% of breast tumors and the diagnosis of which is very rare in patients younger than 20 years. There are no specific symptoms or radiological images to distinguish phyllodes tumor from fibroadenoma; therefore, histological examination is mandatory for diagnosis. Histology also allows the classification of phyllodes tumor into benign, borderline, or malignant types for appropriate surgical treatment: freemargin excision in benign tumors and mastectomy in the other two types. Fortunately, the majority of these tumors are benign, and treatment maximizes breast conservation with free infiltration margins surgery, given that this fact is the most important factor to prevent local recurrence. In this article, we describe a rare case of borderline cystosarcoma phyllodes in a 12-year-old girl.     

Phyllodes tumors of the breast

Opinion statement Phyllodes tumor is a rare fibroepithelial neoplasm of the breast with a very variable, but usually benign, course. Formerly known as cystosarcoma phyllodes, the designation “phyllodes tumor” with appropriate qualification regarding malignant potential based on pathologic features is now the agreed-upon term. The most important diagnostic distinction is from fibroadenoma—phyllodes tumors require complete excision with free margins even when pathologic features suggest benignity because of a proclivity to local recurrence. The most important component of therapy is wide surgical excision, and mastectomy is necessary only when free margins cannot be achieved without it. Involvement of axillary nodes is rare, and axillary dissection is not indicated. The role of radiation therapy and chemotherapy is not established and has not been studied in randomized trials due to the rarity of the tumor. At present, there is no consensus that patients with high-grade phyllodes tumors of the breast will benefit from either of these modalities.     

The effect of systemic therapy on local-regional control in locally advanced breast cancer.

One hundred and seven patients with locally advanced breast cancer were prospectively referred for multimodality treatment on protocol using chemohormonal therapy to maximal response followed by local treatment and maintenance therapy. Forty-eight patients (45%) were diagnosed with Stage IIIA disease, 46 (43%) with Stage IIIB inflammatory cancer, and 13 (12%) with Stage IIIB non-inflammatory disease. Induction therapy consisted of cyclophosphamide, doxorubicin, methotrexate, and 5-fluorouracil with hormonal synchronization using tamoxifen and conjugated estrogens. Local treatment was determined by response to chemotherapy. Patients with a clinical parital response underwent mastectomy followed by local-regional radiotherapy while patients with a clinical complete response were biopsied for pathologic correlation. Those with residual disease received mastectomy followed by radiotherapy while those with a pathologic complete response received radiation only to the intact breast and regional nodes. With a median follow-up of 64 months, patients with IIIA disease had a significantly lower local-regional failure rate compared to IIIB inflammatory patients, with the 5-year actuarial local-regional failure rate as only site of first failure 3% for IIIA disease versus 21% for IIIB inflammatory cancer (p = .02), and local-regional failure as any component of first failure 12% versus 36% (p = .01), respectively. When local-regional failure was analyzed by repeat biopsy, 5/31 (16%) patients with a pathologic complete response treated with radiation only developed a local-regional failure versus 2/53 (4%) with residual disease treated with mastectomy and postoperative radiotherapy. The 5-year actuarial local-regional failure rate as first site of failure was 23% for radiation only versus 5% for mastectomy and post-operative radiotherapy (p = .07). The response to chemotherapy did not reliably predict local-regional control. Both relapse-free survival and overall survival were significantly better for IIIA versus IIIB patients; stratification by repeat biopsy did not however, significantly affect either relapse-free or overall survival.     

乳腺叶状囊肉瘤320例诊治分析

目的探讨乳腺叶状囊肉瘤临床诊断和治疗方法。方法回顾分析经手术病理确诊为乳腺叶状囊肉瘤的320例患者的诊断和治疗情况。结果行乳腺X片检查121例,B超检查25例,近红外检查21例,针吸细胞学检查42例;15例(12.4%)乳腺X片检查及3例(14.3%)近红外检查诊断为乳腺叶状囊肉瘤。临床诊断正确率为17.5%(56/320),误诊率为82.5%(264/320)。随访253例患者,其中局部复发45例(17.8%),远处转移死亡13例(5.1%)。结论乳腺叶状囊肉瘤诊断需常规病理检查,治疗宜行局部广泛切除或全乳切除。     

Phyllodes tumor of the breast: stromal overgrowth and histological classification are useful prognosis-predictive factors for local recurrence in patients with a positive surgical margin

BACKGROUND: The local recurrence rate of phyllodes tumors is high and ensuring a sufficient surgical margin is considered important for local control. However, the preoperative diagnosis rate of phyllodes tumors is low and we often encounter cases in which a sufficient surgical margin is not achieved, since in routine medical practice the lesion may not be diagnosed as phyllodes tumor until postoperative biopsy of a mammary mass. Furthermore, there are no established therapeutic guidelines for surgical stump-positive phyllodes tumors. We reviewed the outcomes of excision of phyllodes tumors to investigate factors involved in local recurrence and to determine the indication for re-excision in stump-positive cases. METHODS: The subjects were 45 patients treated for phyllodes tumors at our institution from January 1980 to July 2005. Age, tumor size, surgical method, stromal cellular atypia, mitotic activity, stromal overgrowth, histological classification and surgical stump status were analyzed. RESULTS: Median age was 45 years old (range 28-75) and tumor size was 1-17 cm (median 3.5 cm). Pathologic diagnoses were benign, borderline and malignant in 31, five and nine cases, respectively, and the surgical stump was negative in 27 lesions and positive in 15. Median follow-up was 101 months (range 1-273), with local recurrence in six cases and distant metastasis in one. The local recurrence-free rate was 88, 88 and 84% and the disease-free rate was 85, 85 and 81% after 5, 10 and 15 years, respectively. Overall 10-year survival was 97%. In univariate analysis, a positive surgical margin, stromal overgrowth and histological classification were predictive factors for local recurrence after breast-conservation surgery (P = 0.0034, 0.0003, 0.026). A positive surgical stump was the only independent predictor of local recurrence in multivariate analysis (RR 0.086; 95% CI 0.01-0.743, P = 0.012). Stromal overgrowth was a predictive factor for local recurrence in cases with a positive surgical margin (P = 0.0139). CONCLUSION: Wide excision is the preferred therapy for phyllodes tumor and preoperative diagnosis is important for good local control. Re-excision is recommended in cases with a positive surgical margin and stromal overgrowth and malignancy.     

Prognostic factors in cystosarcoma phyllodes. A clinicopathologic study of 77 patients.

The authors studied prognostic factors in 77 patients with primary cystosarcoma phyllodes (CSP) of the breast. Median patient age was 50 years of age, and the median follow-up time was 8 years. Sixteen patients (21%) had distant metastases and subsequently died of CSP. Clinical variables such as age, symptom duration, clinical tumor size, and type of surgery were not of prognostic value. Local recurrence was more common among patients treated with breast-conserving surgery than among those treated with mastectomy. However, there was no significant difference between these two subgroups in terms of distant metastasis-free survival or overall survival. The prognostic significance of several histopathologic parameters was also assessed, e.g., stromal cellularity, stromal cellular atypism, mitotic activity, atypic mitoses, stromal overgrowth, tumor contour, tumor necrosis, and heterologous stromal elements. In a multivariate Cox analysis, the only features that were found to be independent prognostic factors were tumor necrosis (P less than 0.05) and presence of stromal elements other than fibromyxoid tissue (P less than 0.01). In summary, additional studies of prognostic factors in CSP are warranted because of the conflicting results in published reports.