Primary breast tumor characteristics predicting aggressive nodal involvement

BACKGROUND: pN3 breast cancer is historically associated with a poor prognosis, but the biology of aggressive nodal involvement or lymphatotropism is not well understood. METHODS: This retrospective study compares clinical and pathological features for 1347 breast cancer patients with pN0 disease, 560 with pN1 disease, and 100 with > or = 10 positive nodes (pN3 [10] disease). RESULTS: Compared with pN1 disease, pN3 (10) disease was more frequently associated with T3-4 primaries (9% versus 38%, P < or = .001), lobular histology (11% versus 22%, P = .01), and inflammatory cancer (1% versus 5%, P = 0.01). pN3 (10) disease was not associated with early-onset or estrogen receptor-negative breast cancer. The 5- and 10-year overall survival for pN3 (10) patients was 64% and 21%, respectively. CONCLUSIONS: The data indicates that the prognosis for pN3 (10) patients may be improving with current treatment. Molecular pathways governing aggressive lymphatotropism appear to be independent of those associated with early-onset, estrogen receptor-negative breast cancer.     

Immunohistochemical detection of a germline BRCA1 mutation in a breast and ovarian cancer family

Tumours from four individuals in a breast and ovarian cancer family with a known deleterious germline BRCA1 mutation, were analyzed using BRCA1 antibodies. In addition, we examined tumours from 96 female patients with early-onset breast cancer, who were not selected because of any family history. Paraffin-embedded tumour sections were examined by standard immunohistochemical analysis. Three familial tumours from BRCA1 carriers displayed focal negativity. This observation was not seen in a non-mutation carrier from the same family. It was found that 9/96 (9%) early-onset breast tumours had total BRCA1 negativity. In addition, 2/2 (100%) medullary breast carcinomas displayed negativity for both antibodies. Our results indicate that BRCA1 antibodies can discriminate between familial tumours with and without a deleterious mutation from one family. Further mutation studies in early-onset breast cancer group will be necessary to evaluate the use of immunohistochemistry as a rapid, initial screening technique to identify BRCA1 mutations.     

Male breast cancer in patients with a familial history of breast cancer

We describe herein the clinical characteristics of five male breast carcinoma (MBC) patients with a familial history of breast carcinoma (FHBC). Four of these patients suffered from multiple primary cancers, being gastric and prostate cancer in 1, gastric cancer in 1, and asynchronous bilateral breast cancers in 2. The average age of these patients at diagnosis was not lower than that of MBC patients with no such familial history. The aggregation of cancer in these families had three prominent characteristics: (1) The families included women with early-onset breast cancers which had occurred at the ages of 38, 38, and 35 years, respectively, and/or early-onset uterine cancer which had occurred at the age of 35 years. (2) The incidence of multiple primary cancers was significantly higher in the siblings of MBC patients with a FHBC than without. (3) There were many cancers in hormone-related organs in two families.     

MDM4基因rs1563828与乳腺癌发病风险及发病年龄的相关性研究

目的 探讨murine double minute 4(MDM4)基因的单核苷酸多态性rs1563828(C＞T)在早发性乳腺癌人群中的分布、与乳腺癌发病风险的关联性及其与发病年龄的潜在关系.方法 本研究为病例-对照研究.采用飞行时间质谱分析法对124例早发性乳腺癌患者(发病年龄≤35岁)和101名健康对照者进行MDM4基因rs1563828(C＞T)基因型鉴定.采用x2检验比较基因型分布和发病风险的关系,应用非条件Logistic回归分析计算危险度,两组发病年龄比较采用t检验.结果 对照组MDM4基因rs1563828基因型的分布频率为CC 43.6％ (44/101)、CT 42.6％ (43/101)、TT13.9％(14/101),病例组则依次为42.7％(53/124)、46.0％(57/124)、11.3％(14/124);两组差异无统计学意义(x2=0.449,P=0.799).Logistic回归分析表明,在早发性乳腺癌人群中,以rs1563828的CC野生基因型为参照,含T基因型(CT,TT)并未改变乳腺癌的发病危险(OR=1.024,95％ CI:0.581～1.806,P=0.934).在乳腺癌人群中,TT基因型携带者的发病年龄低于CT/CC基因型携带者[(30±4)岁比(32±3)岁,P=0.028].结论 MDM4基因rs1563828(C＞T)多态性可能与早发性乳腺癌人群的遗传易感性关联微弱,尚需进一步明确;其TT基因型可能是发病年龄提前的危险因素.     

COMT基因Val158Met多态性在BRCA1/2基因无突变的遗传倾向乳腺癌中的分布

目的探讨Catechol-O-methyhransferase（COMT）基因Val158Met（G→A）多态性在BRCA1／BRCA2基因无突变的具有遗传倾向乳腺癌人群中的分布及其与乳腺癌发病风险的相关性。方法对114例无BRCA1／BRCA2突变的家族性或早发性乳腺癌患者和121例正常对照者进行COMT基因第4外显子的聚合酶链反应扩增,随后进行DNA直接测序鉴定Val158Met多态的基因型,比较基因型分布和发病风险的关系;相对危险比值比（oddratio,OR）及95％可信区间（confidence interval,CI）应用非条件Logistic回归分析计算。结果COMT基因Val158Met多态的GG,GA和AA基因型在病例组中的分布频率分别为0．58（65例）,0．32（36例）和0．10（11例）;在对照组的分布频率分别为0．60（66例）,0．37（41例）和0．03（3例）。在早发性乳腺癌人群中,含A基因型的频率为0．57（21例）,显著高于家族性乳腺癌的0．35（26例）（P=0．026）。以GG基因型为参照,AA基因型（158Met）显著提高了乳腺癌的发病危险（OR=3．15;95％CI：0．70～14．19）（P=0．039）,在绝经前妇女尤为明显（OR=9．98;95％CI：1．00～99．64）（P=0．004）;在体质指数（body mass index,BMI）≤23kg／m^2的妇女中,AA纯合基因型（158Met）临界显著提高了乳腺癌的发病危险（OR=7．57;95％CI：0．57～101．28）（P=0．056）。结论COMT基因Val158Met可能与乳腺癌、特别是绝经前或早发性乳腺癌的遗传易感性有关,可作为低外显率的乳腺癌易感基因位点。     

BRCA mutations, molecular markers, and clinical variables in early-onset breast cancer: a population-based study

Early age at onset is generally considered an indicator of genetic susceptibility to breast cancer. To address both the proportion of early-onset breast cancer associated with BRCA-1 or BRCA-2 germline mutation and the contribution of germline mutations to the clinical features and outcome of these tumors, we analyzed molecular status and clinical variables of a population-based sample of 66 Italian women diagnosed with breast cancer before the age of 40 who were unselected for family history. BRCA mutations were screened by automated sequencing of the entire BRCA-1 and BRCA-2 coding regions and splice junctions. Twenty-eight late-onset (over 45 years), sporadic, breast cancers were designated as "control group" for comparisons with early-onset cases. BRCA mutations (10 BRCA-1 and 6 BRCA-2) were detected in 15 (22.7%) out of 66 tested patients. The combination of ER, PR, HER-2/neu negativity and p53 positivity was significantly more frequent in BRCA-1 positive tumors than in BRCA-2 positive and non-BRCA tumors (P=0.03). Taken collectively, BRCA-positive tumors correlated with high histologic grade and ER negativity compared with non-BRCA and sporadic tumors (P=0.05 and 0.003, respectively). There were no significant differences between BRCA-associated breast cancers (BABC) and non-BABC in relapse-free, event-free, and overall survival. Our data confirm that the combination of age at onset and tumor phenotype can provide an efficient model for identifying individuals with a high probability of carrying BRCA mutations and support the hypothesis that breast cancer in BRCA carriers is qualitatively distinct from other early-onset breast cancers and from late-onset, sporadic, breast carcinomas. Further studies on incident cases are necessary to define the independent prognostic significance of germline BRCA mutations.     

Age-related differences in breast cancer stage at diagnosis between black and white patients in an urban community hospital

Background: Breast cancer mortality is significantly higher among black patients compared to white patients. Black women are reportedly at increased risk for early-onset breast cancer. Our goal was to evaluate stage distribution relative to age among black and white breast cancer patients in an institution with a relatively high minority patient population. Methods: We evaluated 425 patients diagnosed with breast cancer between 1990 and 1994: 56% white, 34% black, the remainder were other ethnicities. Patients were stratified by age: under 50 years versus 50 and older. Socioeconomic status was estimated by utilization of medical care in the private-practice setting versus the public clinic. Results: Significantly more black patients were younger at diagnosis compared to white patients (32% vs. 20%; p=0.008). There was a significantly more advanced stage distribution among the younger black patients, but not among the older black patients. Most of the black and white patients received private-practice care. Conclusions: These age-related differences in breast cancer stage distribution between black and white patients (which appeared independent of socioeconomic status) indicate that more aggressive screening and public education progams directed toward younger black women is warranted, and they lend support to the possibility of ethnicity-related variation in primary tumor biology.     

Incidence of lobular carcinoma in bilateral breast cancer

The histology and clinical records of 52 patients with bilateral breast cancer recorded in a community tumor registry were reviewed. Previous studies have demonstrated the propensity of lobular carcinoma to occur bilaterally. This view is supported by the large number of lobular cancers found in our patients. Thirty-six percent of the patients with bilateral disease had lobular cancer in at least one breast. Those with lobular cancer tended to be younger and more likely to have simultaneous cancers than did patients with nonlobular carcinoma. In those patients in whom the occurrence of tumors was not simultaneous, they were smaller in the second breast but had similar rates of axillary metastases. This study raises the question of how best to manage the contralateral breast in patients with breast cancer. Lobular carcinoma is one marker of the likelihood for development of disease in the second breast; but if advantage is to be gained by this finding, investigation of the opposite breast is best done early. Finally, thorough examination of patients with nonlobular carcinoma must not be ignored because they still comprise the majority of bilateral breast cancers.     

The clinical utility of Tc-99m sestamibi scintimammography in detecting multicentric breast cancer.

The ability to recognize multicentric breast cancer preoperatively would assist in identifying appropriate candidates for breast conservation surgery. Tc-99m scintimammography (SMM) is an adjunct to conventional mammography in identifying selected patients with breast cancer. The purpose of this study is to report the utility of SMM in identifying patients with multicentric breast cancer. Breast cancer patients treated by mastectomy who underwent a preoperative SMM between 1992 and 1999 were identified using the institution's Tumor Registry. The pathology report of each patient was reviewed for multicentric disease defined as an additional focus of cancer within a different quadrant of the breast or greater than 2.5 cm from the dominant tumor mass. Each patient's preoperative SMM was reviewed and compared with the pathologic findings to obtain correlative data. Fifty-eight women treated by mastectomy had preoperative SMM (age range 35-78 years; median 52 years). Pathology revealed infiltrating ductal carcinoma in 49 patients (84.5%), infiltrating lobular carcinoma in five patients (8.6%), ductal carcinoma in situ in three patients (5.1%), and colloid carcinoma in one patient (1.7%). Multicentric disease was present in the specimens of eight patients for a prevalence of 10.3 per cent. SMM was positive for uptake in 36 of 58 patients (sensitivity 62.1%). The sensitivity, specificity, positive predictive value, and negative predictive value of SMM in the detection of multicentric disease were 62.5, 96, 71, and 94 per cent, respectively. Although the overall sensitivity of SMM in the detection of breast cancer is superior to that of conventional mammography and physical examination in identifying multicentric breast cancer it is not an accurate modality for detecting multicentric disease in this study group. However, it may have limited applications in specific cases.     

The impact of microinvasion on axillary node metastases and survival in patients with intraductal breast cancer

A rational approach to the local treatment of intraductal breast cancer continues to generate considerable debate. However, the finding of an invasive component in intraductal breast cancer is widely regarded as an appropriate indication for axillary node dissection as part of the local treatment and staging of this disease. Despite this view, the natural history of patients with intraductal breast cancer with foci of microinvasion is poorly defined. Between 1965 and 1988, 41 patients with this pathologic finding of intraductal carcinoma with foci of microinvasion were seen at the UCLA Medical Center. Twenty-three patients presented with mammographic abnormalities, while 17 patients presented with a palpable mass. One patient presented with Paget's disease of the nipple. Thirty-three patients underwent axillary node dissection as part of their local treatment. No lymph node metastases were identified. The median follow-up in 37 patients was 47 months. There have been no local recurrences and no deaths from recurrent breast cancer. Intraductal breast cancer associated with microinvasion appears to be an extremely favorable lesion with minimal risk of nodal metastases.     

Bilateral synchronous breast cancer: mode of detection and comparison of histologic features between the 2 breasts

BACKGROUND: Bilateral synchronous breast cancer is uncommon (accounting for 1.0%-2.6% of all patients with breast cancer), and most physicians do not accumulate a large personal experience of patients with this disease. We reviewed our experience with patients with bilateral synchronous breast cancer, focusing on the mode of detection and histologic features in the 2 breasts. METHODS: The charts of patients who were treated at this institution for bilateral synchronous breast cancer during the 15-year period of 1984 through 1999 were reviewed. Information regarding age, mode of detection, histopathologic features, treatment, and overall survival were analyzed. RESULTS: During the study period, 51 patients (all women) were treated at our institution for bilateral synchronous breast cancer. This comprised 2.1% of all patients (n = 2382 patients) treated for breast cancer during the same period of time. The first cancer was detected by palpation in 81% and by mammography in 14%. The corresponding figures for the contralateral cancer were 24% and 54%, respectively. The histologic type of cancer was identical in the 2 breasts in 29 patients (57%) and was different between the 2 breasts in 22 patients (43%). The overall 10-year survival rate was 63%. CONCLUSIONS: Bilateral synchronous breast cancer is often detected by mammography and is frequently of the same histologic type as the index cancer. A better awareness of the risk for this disease may help detect bilateral breast cancer earlier.     

Management of cancer of the opposite breast following breast preservation.

Breast preservation has been shown to be a good alternative to mastectomy in selected patients with breast cancer. The purpose of this study was to evaluate the characteristics of cancer developing in the opposite breast to determine if breast preservation should be attempted in that breast as well. From 1979 to 1988, 172 women underwent tylectomy, axillary dissection and irradiation for carcinoma of the breast. All had follow-up mammogram. Mean age was 55 years. Mean follow-up time was 50 months. Thirteen patients (7.6%) developed cancer in the opposite breast. Three cancers were carcinoma in situ, nine were stage I, and one was stage IIa. Nine of 13 patients had breast preservation therapy, and four had mastectomies. Ten patients are alive with no evidence of disease, two are alive with disease and one died with disease. Breast preservation for bilateral breast cancer is a safe alternative if patients can be followed closely.     

Clinical Observations from a Breast Cancer Registry in Asian Women

Background The incidence of breast cancer in Singapore, reflecting cancer trends of developed nations, is rising rapidly. It is the most common cancer in Singaporean women. Given the significant problem that breast cancer poses, this study reports the clinical-pathologic features of 1,165 women with invasive breast cancer managed at a university teaching hospital in Singapore. Methods All patients who were diagnosed, treated, and followed-up at this institution between 1990 and 2002 were analyzed. Data were obtained from the National University Hospital Breast Cancer Registry. Results Of our patients, 82% were ethnic Chinese. The median age of presentation was 49 years, and 24.5% of our patients presented with stage I disease. In addition, 51% of premenopausal and 60% of postmenopausal patients stained positive for estrogen receptor. Mastectomy was the most common surgical therapy, and about 90% of patients received adjuvant therapy. At a median follow-up of 81 months, the median 5-year survival was as follows: stage I, 97%, stage II, 78%, stage III, 52%, and stage IV, 13%. Conclusions This study supports what has been observed among breast cancer patients in this region and reflects a profile of breast cancer that differs from that seen in the West: patients present at a younger age, with more advanced stage and fewer estrogen-positive tumors. Most women in our series received systemic adjuvant therapy, and the 5-year overall survival rates are equivalent to published results from the West. The unique features of the disease in women in Singapore are important to recognize, as they may influence future prevention and management strategies for Asian women with breast cancer.     

The relationship of breast cancer risk with parity and breast feeding in Thai women

An investigation was carried out in 1265 Thai women around the Phyathai area in Bangkok to find out the relationship of breast cancer risk with parity and breastfeeding. The patients studied included individuals who had no clinical evidence of breast disease, those who had benign disease, and those who had breast cancer. With regard to marital and pregnancy status, the finding is in agreement with earlier reports that marriage, pregnancy, and early delivery have a protective role against breast cancer. Breast cancer patients had a higher number of children, a higher percentage of mothers who nursed them, and a longer period of nursing than did normal individuals. These findings differ from earlier reports. Breastfeeding may have a protective role in this disease. It is, however, inconclusive whether a long period of nursing gives protection from breast cancer.     

Laparoscopic oophorectomy in the management of breast disease

Background: Oophorectomy is being increasingly carried out in the management of breast disease, as either adjuvant treatment for breast cancer or for prevention of ovarian and fallopian tube cancer in BRCA gene mutation carriers. The aims of this study were to determine the surgical outcome of laparoscopic oophorectomy when carried out by breast surgeons and whether laparoscopic oophorectomy can be safely carried out during the same anaesthesia as breast surgery. Methods: Patients who had laparoscopic oophorectomy carried out by two breast surgeons were reviewed with regard to the indication, surgical outcome and concurrent procedures. Salpingectomy was also carried out when the indication was prevention. Results: Seventy patients with breast disease had laparoscopic oophorectomy between January 2000 and June 2007. Forty‐three patients had laparoscopic oophorectomy for adjuvant endocrine treatment of early breast cancer, 13 for prophylaxis, 7 for endocrine and prophylactic reasons and 7 for treatment of metastatic breast cancer. Sixteen patients had laparoscopic oophorectomy and breast surgery at the same time, without complication. Of note, four BRCA mutation carriers had prophylactic mastectomies, bilateral breast reconstruction and bilateral laparoscopic salpingo‐oophorectomy. No patient required conversion to an open procedure, including 29 patients with previous abdominal surgery. There were no significant complications. Three patients had ovarian cancer or breast cancer detected in an ovary. Conclusion: Laparoscopic oophorectomy can be safely and efficiently carried out by breast surgeons with expertise in laparoscopic surgery. Previous abdominal surgery did not prevent a successful laparoscopic approach. Breast oncological and/or reconstructive surgery and laparoscopic oophorectomy can be reliably carried out as a combined procedure.     

Are positive axillary nodes in breast cancer markers for incurable disease?

OBJECTIVE: This study was designed to determine if resection of positive regional nodes in patients with breast cancer provided a group of cured patients. SUMMARY BACKGROUND DATA: Previous studies of long-term follow-up of patients with breast cancer have demonstrated that 30% of patients with positive nodes may be alive at 10 or 20 years. Randomized, prospective studies have not shown a difference in survival between modified radical and total mastectomy. METHODS: The authors analyzed the statistical basis of randomized, prospective studies of breast cancer. Patients from University and Kings County Hospital with breast cancer were observed (n = 1024) and the 10-year survival curves were analyzed. Data from the Surveillance, Epidemiology, and End Results (SEER) program were evaluated to determine the prognosis of patients with positive-node breast cancer who survived 10 and 15 years. RESULTS: The authors found that no current randomized study of primary treatment of breast cancer has the power to determine the advantage of one treatment over another if the primary cancer is treated. Additionally, evaluation of the patients in this study demonstrated that those with regional disease usually had a recurrence by 7 years; however, at 10 years, 30% are still alive and have the same prognosis as patients with negative-node breast cancer. CONCLUSIONS: Regional breast cancer is a curable disease in some resected patients.     

Primary tumor resection in patients with stage IV breast cancer: 10-year experience

The role of surgery in the management of stage IV breast cancer is controversial. Existing studies in Stage IV breast cancer have not closely evaluated the role of patient response to induction systemic therapy (IST) in its relationship to survival outcomes. We identified all patients with a diagnosis of de novo stage IV breast cancer who underwent surgery of their primary tumor from January 2008 to December 2018. Patients were grouped according to their response in the primary disease site into progression (progressive primary disease) or no progression (nonprogressive primary; comprising complete, partial and stable response). We identified a total of 45 stage IV breast cancer patients who underwent operative intervention of their primary breast tumor. Prior to surgical intervention, progression in the primary site during IST was identified in 13/42 patients (31%), of whom four patients also had progression in the distant disease. The 5-year survival was higher in the nonprogressive primary (74%) than the progressive primary disease group (52%) which did not reach statistical significance (p = 0.08). Age, pathologic tumor size, clinical nodal status, number of positive lymph nodes, and distant disease response to systemic therapy were significantly associated with survival. In this single institution experience, select patients with stage IV breast cancer at initial diagnosis who underwent resection of the primary tumor following systemic therapy achieved favorable overall and distant progression-free survival. Surgery is reasonable to consider for local palliation or in selected patients who have excellent response to systemic therapy and good performance status.     

Imaging methods in breast diagnosis--value and choice of methods in general practice

X-ray mammography continues to represent the most efficient imaging method for the diagnosis of breast disease and ultimately reduce mortality from breast cancer. Ultrasound is the most valuable supplementary method and is particularly useful to differentiate cystic from solid lesions. Today it is used mostly in the dense breast, as e.g. in young patients. All other imaging methods as thermography, diaphanoscopy, computed tomography and magnetic resonance imaging have not gained any importance and are particularly not useful for screening a large number of patients. In this paper all these imaging methods and our personal experience with them are briefly discussed. The importance of implementing mammographic screening programs to detect breast cancer is stressed, particularly considering the high incidence of breast cancer in all industrialized countries.     

乳腺癌的相关因素

我院１９８０～１９９３年收治的１４２４例乳腺癌患者中女性１４１３例，与其相关因素进行分析。其中停经年龄＞４５岁１１９３例（８４．４％），行经时间≥３０年８４０例（５９．４％），初产年龄＞２５岁９８０例（８０．５％），无哺乳史９１２例（７４．９％）。结果提示：乳腺癌的发生与遗传、其它乳腺疾病、精神因素及头发中微量元素有一定关系。通过对乳腺癌及其相关因素的研究，可望为乳腺癌的治疗及预防开辟新途径。