Multicentric breast cancer: clonality and prognostic studies

Clonality of multicentric breast cancer has traditionally been difficult to assess. We aimed to assess this using analysis of TP53 status (expression and mutation status). These results were then incorporated into an analysis of prognostic factors in multicentric tumours in a 10-year follow up study. Clonal status of multicentric breast cancer foci (n = 88 foci) was determined by immunohistochemical and molecular studies of TP53 in a total of 40 patients. Prognostic factors from these patients were also compared with 80 age- and stage-matched controls with unicentric breast cancer from the Royal Marsden NHS Foundation Trust Breast Cancer Database. Our results indicate that multicentric breast cancer foci were polyclonal within an individual patient in at least 10 patients (25%) with respect to immunohistochemical staining and in four patients (10%) with respect to abnormal band shifts on single strand conformational polymorphism (SSCP) molecular analysis. No individual variable was predictive of multicentric or unicentric disease. However, there was a worse overall survival in the multicentric breast cancer patients in whom at least two cancer foci stained positively on TP53 immunohistochemistry compared with the matched control group (P = 0.04). In conclusion, these results suggest that a proportion of multicentric breast cancer foci are polyclonal with respect to TP53 status and that TP53 over-expression predicts for a poorer prognosis in multicentric breast cancer.     

Prognostic-significance of multifocality in primary breast-cancer

The impact of multicentricity in primary breast cancer on relapse or death after radical or modified radical mastectomy was evaluated in 1336 consecutive patients. Multiple tumor foci were found in 11.7% of breast cancers: in 8.4% multicentricity was infiltrating, while in 3.3% of cases an in situ growth pattern was observed. There was a statistically significant association between multicentric primaries and lobular infiltrating carcinoma, age less than or equal to 50 years, large tumors and metastatic axillary nodes, while no relationship was observed with histological grade. Both 5-year disease-free survival and overall survival were shorter in patients with infiltrating multicentric primary tumors. Multivariate analysis confirmed the prognostic role of infiltrating multicentric tumors after adjusting for nodal status, tumor size, age and adjuvant therapy.     

Breast carcinoma in pregnant women: assessment of clinicopathologic and immunohistochemical features

BACKGROUND: Breast carcinoma is one of the most common carcinomas in pregnant women. The incidence of breast carcinoma may increase in the future because of the trend toward delayed childbearing and increased screening. However, very few contemporary studies have attempted to identify the combined histopathologic and immunohistochemical features of breast carcinoma in these patients. METHODS: The authors evaluated 39 patients with breast carcinoma occurring coincident with pregnancy. This was comprised of a critical histologic review and immunohistochemical evaluation to determine the status of prognostic and predictive markers including estrogen receptor (ER), progesterone receptor (PR), HER-2/neu, Ki-67, and p53. RESULTS: The mean age at presentation was 33 years (range, 24-44 years). Densities and/or masses were noted on mammograms in 14 of 16 patients with available radiographic information. The primary tumors were a mean of 4.5 cm in greatest dimension (range, 0.1-13.5 cm). Two of the 39 patients had clinical (American Joint Committee on Cancer) Stage I disease, 19 patients had Stage II disease, 16 had Stage III disease, and 2 patients had Stage IV disease at the time of presentation. Histologically, high-grade invasive ductal carcinomas were found in 32 of 38 patients. The primary tumor was not available for review in one patient. A predominantly solid pattern of growth was observed in nine patients. Lymphovascular invasion was identified in 61% of cases. Ductal carcinoma in situ was identified in 72% of tumors and was high grade in all cases. Of the 25 patients tested, ER positivity was found in 7 patients, PR positivity was found in 6 patients, HER-2/neu positivity was found in 7 patients, and p53 positivity was found in 12 patients. The proliferation rate as shown by Ki-67 staining was high in 60% of the cases. Follow-up information was available for 35 patients and the mean follow-up period was 43 months (range, 2-163 months). Distant metastasis occurred in seven patients. The mean time to disease recurrence was 20.4 months (range, 10-33 months). Of 35 patients, 4 have died, 22 were alive with no evidence of disease, and 9 were alive with disease at the last follow-up. The remaining four patients died of unknown causes. CONCLUSIONS: Pregnant women with breast carcinomas generally present with advanced-stage disease and the tumors have poor histologic and prognostic features. The findings from the follow-up indicated that these tumors do not follow a very aggressive clinical course as was proposed in earlier reports. Breast carcinomas occurring during pregnancy share many histologic and prognostic similarities with breast carcinoma occurring in other young women.     

Prognosis in T2N0M0 stage I breast carcinoma: a 20-year follow-up study

In a study of prognosis in node-negative breast carcinoma, we investigated 293 T2N0M0 patients treated by mastectomy and axillary dissection with a median follow-up of 19.8 years. The probability of surviving 20 years considering all causes of death was 41.3% +/- 3.0%. Recurrence-free survival (Kaplan-Meier estimate) was 68.6% +/- 3% at 10 years and 63.2% +/- 3.1% at 20 years. The estimated probability of cure determined by the method of Brinkley and Haybittle was 63% (95% confidence interval [Cl], 55% to 72%). Prognosis was related to primary tumor size with the best separation (P = .06) when tumors from 2.1 to 3.0 cm (33% chance of recurrence at 20 years) and from 3.1 to 5.0 cm (44% chance of recurrence at 20 years) were compared. The histologic tumor type was prognostically important. Recurrence at 20 years was not significantly different for patients with invasive duct (34%) and lobular (42%) carcinoma. Women with special types (medullary, mucinous, papillary, etc) of carcinoma had a 25% chance of recurrence. Subsequent contralateral breast carcinoma was diagnosed in 29 patients, and four of these were fatal, accounting for only 4.6% of breast carcinoma deaths. Thirty-two patients (10.9%) developed a nonmammary malignant neoplasm (NMMN) after the ipsilateral breast carcinoma, and 69% of these lesions were fatal. Although the chances of recurrence at 20 years related to tumor size and type did not differ statistically in the series, there were trends that suggest that T2N0M0 patients can be stratified into recurrence risk groups based on tumor size and histologic type. These factors should be taken into consideration in the design and analysis of clinical adjuvant therapy trials. Measures for the early detection of common NMMNs should be included in the routine follow-up of T2N0M0 breast carcinoma patients.     

Cancerous residue in breast-conserving surgery

Local tumor extension was studied using a continuous series of multiple blocks of mastectomy specimens to assess malignancy remaining after breast-conserving surgery for early-stage breast cancer. In this study, 183 cases were chosen, consisting of 6 noninvasive ductal carcinoma cases and 177 invasive ductal carcinoma cases. The histopathology in 59 (32%) of the 183 cases corresponded to that showing extensions of more than 2.6 cm from the tumor margin. These wide extensions were also seen in 17% of breast cancers with a tumor size of less than 2 cm. The incidence of wide extension was higher in younger patients with cases of noninvasive ductal carcinoma. Extension to the nipple-areola was seen in 14% of cases with a tumor size of less than 2 cm. Breast cancers with multicentric development accounted for 3% of those with a tumor size under 2 cm. These findings suggest that if lumpectomy is performed with a margin of 2 cm for tumors with a size of 2 cm or less, a cancerous residue would be found in the surgical margin of 15–20% of the cases. The actual incidence was 23% of cases after breast-conserving treatment in our study. On the basis of the data, breast-conserving treatment with only local resection of the primary lesion showed cancerous residue such as intraductal cancerous extension in about 20% of cases. Therefore, it was concluded that, as part of breast-conserving therapy of early-stage breast cancer, radiation therapy of the whole breast should be performed after surgery with clear margins to Control local recurrence. © 1993 Wiley-Liss, Inc.     

Breast carcinoma in women age 25 years or less

BACKGROUND: Although several studies have examined breast carcinoma in young women aged < or = 35 years at diagnosis, there are only occasional cases reported in very young women aged < or = 25 years, and, to the authors' knowledge, no series are available. The presentation, tumor biology, behavior, and outcome of breast carcinoma in very young women are not known, and the rarity of breast malignancy within this age group could lead to diagnostic delays. METHODS: The tumor characteristics and survival of 15 women aged < or = 25 years at the time of diagnosis, have been reviewed and compared with women aged 26-35 years under the care of Guy's Hospital's Breast Unit during the same period of time. Where appropriate, the two groups were individually matched for tumor size (clinical measurement) and histologic grade. RESULTS: Fifteen cases were examined, with a median follow-up of 108 months and a median age of 24 years. The median duration of symptoms was 4 weeks, and the median tumor size was 20 mm. Two patients had ductal carcinoma in situ (DCIS) only, while the other 13 patients had invasive carcinomas, none of which were Grade I. A mastectomy was performed on 8 out of 15 patients (53%). Axillary nodal metastases were present in 4 out of 12 patients (33%). Of the 13 cases of invasive disease, 9 out of 13 patients (69%) experienced recurrence and died of breast carcinoma. Median disease free survival for patients with invasive disease was 86 months. There was no difference in overall survival between the patients aged < or = 25 years and those aged 26-35, but taken together young women < or = 35 had a worse prognosis than women between 36 and 65, due to a higher incidence of high grade and estrogen receptor negative tumors. CONCLUSIONS: The current study suggests that among young women with breast carcinoma there is no difference in prognosis between the very young and the young. Despite two thirds of patients being node negative, the high mortality rate indicates a need for an optimal selection of adjuvant therapy among these cases.     

Unilateral Multicentric Breast Carcinoma Studied by Whole Mammary Gland Serial Sectioning

The incidence and clinicopathologic features of unilateral multicentric breast cancer (UMBC) were studied by mammary gland serial sectioning in 116 cases of clinically defined monocentric breast cancer (MONBC) examined histopathologically at the Nagano Cancer Detection Center. UMBC was defined as: 1) histopathologically discontinuous tumors each with an intraductal spread, 2) at least one tumor-free section separating two tumors, and 3) a large primary tumor and other small secondary tumors. UMBC was detected in 23 of 116 cases (19.8%), all with one secondary tumor. Primary and secondary tumors were located in the same quadrant in 34.8% and in different ones in 65.2%. The secondary tumors were <5 mm in size in 56.5%. Secondary tumors, averaging 8.3 mm in size and 25.5 mm in distance from the primary tumor, were almost exclusively noninvasive carcinomas, including 15 (65.4%) noninvasive ductal carcinomas and several special types. The primary and secondary tumors were of the same histologic type in 3 of 23 cases. UMBC patients averaged 6 years younger than MONBC patients, and the incidence of UMBC tended to be higher in younger patients (p<0.1). UMBC tended to occur more frequently in quadrant with an average histologie tumor size significantly smaller than that in MONBC (p<0.01). The histologie types of the primary tumor in UMBC and MONBC were similar, with common types predominant. Lymph node metastases tended to be slightly more frequent in MONBC. This high incidence of UMBC calls for careful attention when considering breast conserving therapy.     

乳腺包被性乳头状癌的临床病理分析

目的 探讨乳腺包被性乳头状癌（encapsulated papillary carcinoma, EPC）的临床病理学特征、诊断、治疗及预后。方法 回顾性分析新疆医科大学附属肿瘤医院病理科2010年1月-2013年12月间,诊断为囊内乳头状癌或包被性/包裹性乳头状癌35例及48例对照组导管内乳头状癌的临床病理资料及免疫表型。结果 EPC患者均为女性,年龄29~83岁,平均61岁,肿块大小平均2.4 cm (范围0.6~4 cm)。35例EPC中,22例为单纯性EPC、7例伴导管原位癌、4例伴微小浸润癌、2例伴非特殊类型浸润癌。35例EPC与48例导管内乳头状癌病变内部均未见肌上皮细胞,CK5/6及p63肌上皮染色结果显示,EPC病变周围肌上皮数量较导管内乳头状癌导管壁肌上皮数量明显减少,差异具有统计学意义（P<0.05）;35例EPC中80%激素受体阳性,5.71%HER2表达阳性。8例（22.86%）EPC患者行肿块切除,27例（77.14%）患者行乳房切除术,3例（8.57%）发生淋巴结转移。术后经随访2~48月,患者均存活。结论 乳腺包被性乳头状癌是一种好发于老年女性的恶性肿瘤,病变周缘肌上皮明显减少甚至缺如,单纯性EPC也可发生淋巴结转移,被认为是一种惰性的浸润癌,生物学行为介于原位癌与浸润癌之间。若单独发生或伴随原位癌及微小浸润癌时,应参照原位癌治疗, EPC伴随浸润癌时,应参照浸润癌的治疗标准进行。     

Metaplastic carcinomas of the breast.

BACKGROUND AND OBJECTIVES: Metaplastic carcinomas of the breast are rare neoplasms. The purpose of the present study is to better characterize the clinical course, treatment, and prognostic factors of metaplastic breast carcinomas. METHODS: Data of 14 patients with metaplastic breast carcinoma were retrospectively reviewed. The follow-up period ranged from 2 months to 10 years, 10 months (median 4.3 years). RESULTS: The patients' ages ranged from 38 to 66 years (median 50.5 years). The tumors were 2.5 to 18 cm (median 4.8 cm) in size. Seven patients had axillary nodal metastases at the time of diagnosis. Estrogen and progesterone receptors were positive in only one tumor. Twelve patients underwent modified radical mastectomy and two patients underwent incisional biopsy. Adjuvant chemotherapy was administered to six patients, and radiotherapy to two patients after mastectomy. Two patients received preoperative chemotherapy. Seven patients were living without evidence of disease at a median of 7.3 years after surgery. A patient died of ovarian carcinoma without recurrence or metastasis of breast cancer. Metastases occurred in five patients at 4 to 16 months (median 8 months) after initial treatment. Duration of symptoms, TNM stage, tumor size, and axillary nodal status were significant prognostic factors of survival. CONCLUSIONS: The patients with metaplastic breast carcinomas may have a favorable prognosis.     

Proliferation index in various stages of breast cancer determined by Ki-67 immunostaining.

To investigate factors involved in progression of breast cancer, we estimated the growth fraction of malignant cell populations in various stages of mammary cancer growth. Frozen sections were immunostained with the Ki-67 monoclonal antibody and the proliferation index determined using static image analysis. Pure intraductal carcinoma, intraductal carcinoma coexisting with invasive disease, and metastatic sites coexisting with primary tumors were studied. The proliferation index of pure intraductal carcinomas (mean 4.5%, median 1.8%) was not significantly different from invasive mammary cancers (mean 5.1%, median 2.2%). The proliferation index determined for the in situ component of primary cancers (mean 3.8%, median 1.5%) was not significantly different from values obtained from the invasive component of growth (mean 4.2%, median 2.1%). Variability between in situ and invasive components for individual cases was minimal in tumors whose proliferation index was less than 3.0%; for tumors with higher proliferation indices, the differences were greater. However, there was no trend toward a decrease or increase in growth fraction for the two components of primary tumor growth. The mean proliferative index for primary tumors (mean 4.9%, median 4.0%) was not significantly different from the mean proliferative score from a matched group of metastatic sites in the same patients (mean 5.7%, median 5.5%). Comparison of individual cases uncovered differences in some tumors; again no consistent trends in either direction were noted. An increase (or decrease) in growth activity does not accompany the transition from intraductal (in situ) disease to invasive mammary cancer, nor does a change in growth fraction necessarily accompany progression of mammary cancer from the primary to regional metastatic site.     

Conservation therapy for breast cancers other than infiltrating ductal carcinoma

Pathologic review of 861 Stage I and II breast cancers yielded 152 patients (18%) with histologic types other than invasive ductal carcinoma. All patients had been treated by breast-conserving surgery and radiotherapy, including supplemental radiation to the tumor bed. For 67 patients with predominantly lobular carcinomas, the actuarial overall 5-year survival was 100% and 77% for node-negative and node-positive patients, respectively. The actuarial probability of recurrence in the treated breast (13.5% at 5 years) appeared to be somewhat greater than that observed after treatment of invasive ductal cancers (8.8% at 5 years, P = 0.11). Of 12 mammary recurrences in patients with lobular carcinoma, four occurred at a considerable distance from the original primary and seven were multifocal, involving more than one quadrant in five patients. Of 47 patients with strictly in situ carcinomas, one patient whose axillary nodal status had not been determined subsequently developed distant metastases. Three additional patients developed mammary recurrence, two at the primary tumor site and one in another quadrant. The actuarial 5-year mammary recurrence and overall survival rates were 4% and 98%, respectively. For 27 patients with true medullary cancers, overall survival at 5 years was 90%. One localized mammary recurrence was observed at the site of the original primary. Actuarial mammary recurrence rate was 4% at 5 years. No relapse was observed in ten patients with colloid and one patient with adenoid cystic carcinoma. The authors conclude that, in addition to its well-established efficacy in the treatment of infiltrating ductal carcinomas, the combination of tumor excision and radiotherapy appears to provide adequate local control for other histologic types as well. However, patients with lobular cancer appear to be at somewhat greater risk of mammary failure, and recurrences in such patients tend to be multifocal and multicentric.     

Therapeutic effect of stage III breast cancer--comparative study of preoperative intra-arterial infusion chemotherapy and non-infusion therapy

Between January 1977 and March 1988, 111 patients of stage III breast cancer were treated in Sapporo Medical College. The median age was 51.6 years (range, 26-83 years). Menopausal status was 47 cases of premenopausal, 19 cases of perimenopausal and 45 cases of postomenopausal. Fifty-seven of these patients received intra-arterial infusion chemotherapy. The anticancer drugs were mainly given by two routes, infusion into the internal mammary artery and the subclavian artery. Continuous infusion of 5-FU and intermittent injections of MMC, ADR or 4'-epi-ADR were jointly or individually made in each artery. Clinico-histological response was studied in 53 out of 57 patients. Clinical response, defined as CR + PR, was noted in 33 patients (62.3%). Histological response according to Shimosato Criteria, defined as grade IIb or better, appeared in 31 patients (58.5%). Non-infusion group contained 27.7% of stage IIIb, against 72.2% in infusion group. The 5-year overall survival rates were; non-infusion group 62%, 5-FU infusion group 34.1%, and ADR MMC group 66.2%. A significant difference was seen between 5-FU infusion group and ADR-MMC group (p = 0.03). The median disease-free interval was 22.0 months (range, 1-77 months) in infusion group and 28.2 months (range, 1-124 months) in non-infusion group. MMC + ADR combination group revealed the most excellent results in terms of the 5 year survival rate and clinicohistological effect.     

Late mortality from pT1N0M0 breast carcinoma.

BACKGROUND: pT1N0M0 breast carcinoma (< or = 2 cm in greatest dimension, lymph node negative) is associated with generally favorable 5-year and 10-year survival, but to the authors' knowledge there are few data available regarding the long term outcome of these patients. METHODS: The authors identified women with breast carcinoma diagnosed between 1945-1984 in a geographically defined urban population using the files of the Finnish Cancer Registry and local hospital records (n = 1495). The clinical and autopsy records and histologic slides were reviewed. The series contained 265 patients with unilateral pT1N0M0 breast carcinoma treated with mastectomy and axillary lymph node dissection without adjuvant systemic therapy and who were followed for 10-44 years (median, 17 years) after the initial diagnosis or until death. RESULTS: The last death from pT1N0M0 breast carcinoma occurred 23 years after the initial diagnosis. The 20-year overall survival rate was 54% (95% confidence interval [95% CI], 48-60%) and the survival rate when corrected for intercurrent deaths was 81% (95% CI, 75-87%). The 20-year survival rate when corrected for intercurrent deaths was 92% (95% CI, 86-98%) in patients with T1a-b disease (primary tumor < or = 10 mm), but was only 75% (95% CI, 64-86%) in patients with pTc disease (range, 11-20 mm). None of the patients with well differentiated (World Health Organization Grade 1) pTa-b tumors died of breast carcinoma (n = 48) whereas the 20-year survival rate when corrected for intercurrent deaths was 81% (95% CI, 67-95%) in patients with Grade 2-3, pT1a-b tumors (P = 0.002). CONCLUSIONS: Patients with well differentiated pT1a-b tumors form a subgroup with excellent long term prognosis, but a significant proportion of women with either moderately or poorly differentiated pT1a-b tumors or pT1c tumors ultimately die of the disease.     

Are prognostic factors for local control of breast cancer treated by primary radiotherapy significant for patients treated by mastectomy?

Recent follow-up studies of patients with mammary carcinoma treated with breast-conserving primary radiotherapy identified a triad of pathologic features significantly associated with local treatment failure. These unfavorable characteristics of the primary tumor were: poor or undifferentiated nuclear grade; intraductal carcinoma within the tumor mass; and intraductal carcinoma in breast tissue outside the perimeter of the primary lesion. The current study was undertaken to assess the impact of these same factors on the prognosis of 573 consecutively treated women, with invasive duct carcinomas 5 cm or less in diameter, and who underwent mastectomy. Histologic sections of all primary tumors were reviewed, and the lesions were classified according to the distribution of intraductal carcinoma present: only within the tumor (IN, 247 cases, 43%), only outside the tumor (OUT, 25 cases, 4%), within the outside (IN-OUT, 158 cases, 28%), or not seen (IFDC, 143 cases, 25%). The median follow-up period for the entire series was 56 months. Ninety-five (17%) patients were dead of disease (median time to death, 36 months). Variables that proved to be statistically significant for overall survival were nodal status (P less than 0.001), nuclear grade (P less than 0.03), and histologic grade (P less than 0.007). Nodal status (P less than 0.001), histologic grade (P less than 0.001), and tumor size (P = 0.01) were significant predictors of disease-free survival. The pattern of intraductal carcinoma, when present, was not predictive of the risk for recurrence or survival in women treated by mastectomy. These findings provide a rationale for additional surgical treatment for women whose tumors have features more likely to be associated with local failure following primary radiotherapy. To permit more detailed pathologic examination of the primary lesion, the initial excision should be carried out separately from the treatment when limited resection and radiation are to be considered as a treatment option.     

Mutant p53 protein overexpression in women with ipsilateral breast tumor recurrence following lumpectomy and radiation therapy

BACKGROUND: The p53 tumor suppressor gene encodes a nuclear phosphoprotein that is thought to be important to cell cycle regulation and DNA repair and that also may regulate induction of apoptosis by ionizing radiation. Somatic p53 gene mutations occur in 30-50% of breast carcinomas and are associated with poor prognosis. Mutations in the p53 gene result in prolonged stability of the protein that can be detected by immunohistochemical techniques. In a matched case-control study of breast carcinoma patients with ipsilateral breast tumor recurrence (IBTR) following lumpectomy and radiation therapy, the authors investigated the frequency and prognostic significance of somatic p53 mutations as well as the clinical characteristics of patients with these mutations. METHODS: Between 1973 and 1995, there were 121 breast carcinoma patients with IBTR following lumpectomy and radiation therapy, and the authors identified 47 patients in whom the paraffin embedded tissue blocks from the primary breast tumors were available for further molecular analysis. Forty-seven control breast carcinoma patients from the breast carcinoma data base were individually matched to the index cases who did not have IBTR for age, treatment date, follow-up, histology, margin status, radiation dose, and adjuvant treatment. Immunohistochemistry using a monoclonal antibody to mutant p53 protein was used to determine mutant p53 protein overexpression in breast tumors and appropriately scored. RESULTS: A total of 12 of 47 tumor specimens (26%) from index patients with breast tumor relapses demonstrated mutant p53 protein overexpression, whereas only 4 of 47 specimens from controls (9%) demonstrated high mutant p53 immunoreactivity (P = 0.02). The authors found that 9 of 23 patients (39%) with early breast tumor recurrences (recurrences within 4 years of diagnosis) had overexpression of mutant p53 protein, whereas only 1 of 23 control cases (4%) had high mutant p53 protein immunoreactivity (P = 0.003). In contrast, index cases from patients with late breast tumor relapses (more than 4 years after diagnosis), which are more likely to represent de novo breast tumors, and control cases from the breast carcinoma data base without IBTR had similar levels of mutant p53 protein overexpression (P = not significant). The 10-year distant disease free survival for patients with mutant p53 protein was 48%, compared with 67% for breast carcinoma patients without detection of mutant p53 protein (P = 0. 08). The authors found that 13 of 14 primary breast tumors (93%) with mutant p53 protein overexpression were estrogen receptor negative (P = 0.01) and 11 of 14 (79%) were progesterone receptor negative (P = not significant). CONCLUSIONS: In a matched case-control study, overexpression of mutant p53 protein has prognostic significance with respect to IBTR following lumpectomy and radiation therapy. Breast tumors with p53 mutations are generally estrogen receptor negative and are associated with compromised distant disease free survival.     

Antibodies to mouse mammary tumor virus-related antigen in sera of patients with breast carcinoma

Sera from patients with breast carcinoma, benign breast disease, malignancies other than breast carcinoma, and healthy female controls were analyzed by indirect immunofluorescence for the presence of antibodies directed toward antigens of mouse mammary tumor. Sera from 56 to 137 (40.9%) patients with breast carcinoma were positive. Positive reactivity was also found in sera from 5 to 27 (18.5%) patients with benign breast disease, in 7 of 60 (11.7%) patients with malignancies other than breast carcinoma, and in 2 of 56 (3.6%) female controls. In the group of patients with breast carcinoma a correlation was noted between age and the probability of detection of these antibodies. Histopathologic examination of breast cancers indicated that antibodies to antigens in mouse mammary tumors were more often found in patients with infiltrating ductal carcinoma of the mucinous type than with other types of breast tumors. No correlation was demonstrable between the incidence of detection of these antibodies and the stage of the disease. Immunochemical analyses indicated that the antibody activity was present in IgG and IgM classes of immunoglobulins. The human antibodies to antigens in mouse mammary tumors could be removed from patients' sera by absorption with disrupted mouse mammary tumor virus (MMTV) but not with gp52 or gp34 (52,000 and 34,000 dalton polypeptides) of MMTV, or with Rauscher mouse leukemia virus (MLV).     

Radiofrequency thermal ablation of breast tumors combined with intralesional administration of IL-7 and IL-15 augments anti-tumor immune responses and inhibits tumor development and metastasis

Tumor development or recurrence is always a matter of concern following radiofrequency thermal ablation (RFA) of tumors. To determine whether combining RFA with immunologically active cytokines might induce tumor-specific immune responses against mammary carcinoma and inhibit tumor development or metastasis, we evaluated intralesional injection of IL-7 and IL-15 in RFA-treated murine tumors. We used two different breast carcinoma models: neu-overexpressing mouse mammary carcinoma (MMC) in FVBN202 transgenic mouse and 4T1 tumors in Balb/c mouse. MMC tend to relapse even in the presence of neu-specific immune responses, and 4T1 is a weakly immunogenic, aggressive and highly metastatic transplantable tumor. In vivo growth of both of these tumors is also associated with increased numbers of CD11b+Gr1+ myeloid-derived suppressor cells (MDSC). We showed for the first time that unlike RFA alone, RFA combined with the administration of intralesional IL-7 and IL-15 (after RFA), induced immune responses to tumors, inhibited tumor development and lung metastasis, and reduced MDSC. Mehran Habibi and Maciej Kmieciak have equal contribution to the work.     

The pathological findings of breast cancer in patients surviving 25 years after radical mastectomy

The authors report the findings in 107 women who are known to have survived 25 years from among a population of 746 consecutive patients who underwent radical mastectomy for breast carcinoma at the University of Chicago Hospitals and Clinics from 1929 to 1955. Of these patients, 103 had invasive carcinomas, two had intraductal carcinomas, and two had subareolar papillomatosis. Six patients had to be excluded because of inadequate pathologic material. The pathologic findings in 93 cases were compared with those in an equal number of control cases dying within a comparatively short period (median, 3.4 years; range 0.9-9.9 years) after radical mastectomy. These were matched for age, tumor size, and number of positive nodes. Only two of our patients suffered recurrences, and none died of her original tumor; however, 12 developed second primaries in the opposite breast, and four died from them. Compared with all patients who underwent radical mastectomy in this period, the 25-year survivors were younger (69 versus 43% were younger than age 50 years), had smaller tumors (39 versus 26% less than 2 cm in diameter), and a larger number (60 versus 39%) had negative nodes. Nonetheless, 12% of the survivors had tumors larger than 5 cm in diameter and 11% had four or more positive nodes. Histologically, 19% of the 25-year survivors had medullary, mucoid, infiltrating lobular, tubular or lipid rich carcinomas, whereas there was only one lobular and one apocrine carcinoma in the control group. Compared with controls, the survivors had a higher percentage of Grade I tumors and a lower incidence of lymphatic and vascular invasion in the breast. Only one 25-year survivor compared with 16 controls had blood vessel invasion. A surprising 63% of the 25-year survivors had lymphatic or vascular invasion within the tumor, or lymph node metastases compared with 82% of controls. While our studies confirm the importance of these well-known prognostic indicators, it also shows that some patients with pathologically unfavorable lesions, i.e., large tumors of high grade with extensive lymphatic invasion and many positive nodes, treated by radical mastectomy may survive for 25 years. However, we could not accurately predict, among the cases we studied, who would be expected to survive 25 years or who would die within four years.     

伴印戒细胞成分乳腺癌的临床病理学观察

目的　探讨伴印戒细胞成分乳腺癌的病理特征及诊断 ,鉴别诊断要点。方法　经HE、AB/PAS及免疫组化对 8例伴印戒细胞成分乳腺癌进行观察 ,并文献复习。结果　本组患者均为女性 ,平均年龄 5 4 6岁 ,肿块平均 2 6cm ;组织学以浸润性乳腺癌伴多少不等的典型印戒样癌细胞为特征 ,6 / 8例为浸润性小叶癌 ,其中 5 / 6例ER、PR阳性表达 ;2 / 8例浸润性导管癌 ,1/ 2例ER、PR阳性 ;7/8例癌细胞中印戒细胞成分超过 10 %;4例做AB/PAS均提示印戒细胞浆内的粘液表达 ;印戒细胞成分的多少与病人预后有关系。结论　伴印戒细胞成分乳腺癌是乳腺癌中的一种特殊类型 ,排除转移及与粘液腺癌的鉴别诊断尤为重要。     

125例乳腺浸润性小叶癌的临床特征及预后分析

 目的　分析乳腺浸润性小叶癌的临床特征及预后情况。方法　回顾性分析1990年1月至2008年12月中山大学肿瘤防治中心收治的125例乳腺浸润性小叶癌患者的临床资料,总结其临床特征、复发及生存情况。结果　125例浸润性小叶癌患者的中位年龄45岁（27～76岁）,诊断时肿块超过3 cm者占61.6 %（77／125）,51.2 %（64／125）患者区域淋巴结阳性,80.8 %（101／125）患者为Ⅱ期以上,89.6 %（112／125）患者的激素受体阳性。中位随访58个月（11～222个月）,此时有32例出现复发及转移,18例死亡。生存分析显示,浸润性小叶癌患者的5年无病生存率和总生存率分别为82.2 %和87.3 %。多因素分析显示,是否进行内分泌治疗是影响浸润性小叶癌的唯一预后因素。结论　乳腺浸润性小叶癌患者在发病中位年龄上与其他病理类型乳腺癌无明显差异,诊断时呈现肿瘤较大和淋巴结侵犯较多是该病的一个特点,激素受体阳性率高是该病的另一个特点。临床病理特征的差异没有显著影响患者预后。