Clinical Significance of Occult Micrometastases in Axillary Lymph Nodes in "Node-negative" Breast Cancer Patients

The most important subgroup of breast cancer patients for whom reliable prognostic indicators are needed is women without axillary lymph node metastases. We evaluated the clinical significance of occult micrometastases in axillary lymph nodes in 148 consecutive "node-negative" breast cancer patients. The median age of the patients at surgery was 52 years and the median follow-up period after surgery was 98.5 months. Occult micrometastases were detected in 21 of 148 patients (14.2%) by means of immunohistochemical analysis using AE1/3 antibody and a single unstained section after routine histopathological examination. Log-rank tests indicated that the 7–year disease-free survival (DFS) and overall survival (OS) rates by Kaplan-Meier methods were significantly better in patients without occult micrometastases than in patients with occult micrometastases [DFS, 93% versus 71% ( P =0.0009); OS, 96% versus 76% ( P =0.0001)]. According to Cox's multivariate analysis, the presence of occult micrometastases had the most significant effect on DFS ( P =0.0053) and OS ( P =0.0035). These findings suggest that the presence of occult micrometastases is an independent and significant predictor of clinical outcome, and that their immunohistochemical detection after routine histopathological examination is useful for selecting the "node-negative" breast cancer patient subgroup at high risk for relapse and death.     

Clinical significance of occult micrometastases in axillary lymph nodes in "node-negative" breast cancer patients.

The most important subgroup of breast cancer patients for whom reliable prognostic indicators are needed is women without axillary lymph node metastases. We evaluated the clinical significance of occult micrometastases in axillary lymph nodes in 148 consecutive "node-negative" breast cancer patients. The median age of the patients at surgery was 52 years and the median follow-up period after surgery was 98.5 months. Occult micrometastases were detected in 21 of 148 patients (14.2%) by means of immunohistochemical analysis using AE1 / 3 antibody and a single unstained section after routine histopathological examination. Log-rank tests indicated that the 7-year disease-free survival (DFS) and overall survival (OS) rates by Kaplan-Meier methods were significantly better in patients without occult micrometastases than in patients with occult micrometastases [DFS, 93% versus 71% (P = 0.0009); OS, 96% versus 76% (P = 0.0001)]. According to Cox's multivariate analysis, the presence of occult micrometastases had the most significant effect on DFS (P = 0.0053) and OS (P = 0.0035). These findings suggest that the presence of occult micrometastases is an independent and significant predictor of clinical outcome, and that their immunohistochemical detection after routine histopathological examination is useful for selecting the "node-negative" breast cancer patient subgroup at high risk for relapse and death.     

乳腺癌全乳腺切片的病理组织学研究：Ⅰ.多厚发癌灶

From April 1988 to January 1989, histopathologic studies by whole organ subserial sections was done in 200 mastectomy specimens of female breast carcinoma. Multicentricity was demonstrated in 40 breast, with 68 multicentric lesions, an incidence of 20%. 80% of these 68 foci were clinically occult, measuring less than or equal to 1.0 cm. 72% was histologically noninvasive whereas only 28% invasive. Among the different pathologic types, intraductal carcinoma was more common (66%) than the others. Most (85%) of the multicentric lesions in the breast had one or two foci, rarely more than two. Multicentric lesions are usually distributed in the neighboring one or two quadrants of the primary cancer, seldom throughout three or four quadrants. They were less frequently seen in the same quadrant (22.5%). The multifocal growth was not related to age or menstrual status of the patient.     

A nonsense mutation (E1978X) in the ATM gene is associated with breast cancer

Blood relatives of patients with ataxia-telangiectasia (A-T) have an increased risk to develop breast cancer. Allelic heterogeneity has made it difficult to confirm the role of ATM, the gene mutated in A-T, for breast cancer susceptibility in the general population. We now report that a nonsense mutation, p.E1978X (c.5932G>T), is both a classical A-T mutation and a breast cancer susceptibility allele in Eastern European populations. In a case–control study from Belarus, the E1978X mutation was identified in 10/1,891 Byelorussian breast cancer cases (0.5%) compared with 1/1,019 population controls [odds ratio (OR): 5.4; 95% confidence interval (95% CI), 0.7–42.4, P = 0.1]. A second case–control study from Russia identified the E1978X mutation in two Russian and one Ukrainian cases out of 611 breast cancer patients but not in any Russian or Ukrainian controls (P = 0.1). In a third case–control study from Poland, E1978X was observed in 7/3,910 Polish breast cancer cases (0.2%) compared with 1/2,010 cancer-free population controls (OR: 3.6; 95% CI: 0.4–29.3, P = 0.4). In the combined analysis, E1978X was significantly associated with breast cancer (Mantel–Haenszel OR: 5.6, 95% CI: 1.3–21.4, P = 0.01). Taken together, this study provides first evidence for the association of a common A-T causing mutation with breast cancer in Eastern European founder populations.     

Detection and significance of occult axillary node metastases in patients with invasive breast cancer.

Blocks of axillary lymph nodes from 78 patients with invasive breast cancer, which after "routine" pathological examination were regarded as negative for metastases, were step-sectioned at 20 u intervals. Occult metastases were detected in 24% of the cases. A significant association between such metastases and a lack of or slight degree of an intraductal carcinomatous component of the dominant cancer was noted. There was no relationship between occult metastases and 15 other histopathological and 3 clinical features investigated, including an average 5 year survival rate. Similarly there was no correlation between any of the possible discriminants investigated in the 24% of patients who have died of their diseases or are living with recurrence regardless of the presence of occult metastases. Factors accounting for the lack of universal survival in patients with Stage I (and those with occult metastases that might be designated as stage 11/2) remain enigmatic. It is concluded that attempts to detect occult metastases by extending histopathological methods may be more academic than practical or therapeutically significant.     

56例隐匿性乳腺癌临床病理特征分析及诊疗策略探讨

背景与目的：隐匿性乳腺癌发病隐匿,诊断困难,治疗策略不确定,是乳腺癌领域的难点和热点。本研究探讨了隐匿性乳腺癌的临床病理特征及诊疗策略。方法：对56例隐匿性乳腺癌患者在术前采用乳腺彩超、钼靶、磁共振及PET/CT检查,对比不同检查方法对隐匿性乳腺癌可疑原发灶检出率及病理符合率的差异。治疗方案采用新辅助化疗、乳腺癌改良根治术、保乳+腋窝淋巴结清扫术、腋窝淋巴结清扫术,术后行化疗+放疗。结果：乳腺超声、X线、MRI、PET/CT对乳腺可疑原发灶的检出率分别为7.14%（4/56）、29.41%（15/51）、37.50%（18/48）和16.28%（7/43）;结合术后病理学检查发现其病理符合率分别为66.67%（2/3）、50.00%（7/14）、50.00%（9/18）和50.00%（3/6）;26例患者乳腺超声、X线及MRI均未发现可疑原发灶,其中21例接受病理学检查,阳性率为14.29%（3/21）;对39例乳腺癌改良根治术标本行乳腺病理切片检查,检出原发灶15例,检出率38.46%。根据St. Gallen指南分子分型标准,Luminal A型、Luminal B型、HER-2阳性型和三阴性型比例分别为7.14%、46.43%、12.50%和33.93%。术后随访52例,随访时间10~104个月,中位时间35个月,复发转移4例,死亡0例。检出原发灶的15例患者中,复发或转移2例;未检出原发灶的24例患者中,无复发或转移;行新辅助化疗17例,达病理学完全缓解（pathological complete response,PCR）2例,复发或转移2例;行乳腺癌改良根治术39例,复发或转移2例;行保乳+腋窝清扫8例,复发或转移2例;腋窝清扫9例,无复发或转移。结论：乳腺MRI检查在隐匿性乳腺癌的排除性诊断中有重要价值;乳腺超声、X线及MRI均未发现可疑原发灶的患者其乳腺病理原发灶检出率较低;隐匿性乳腺癌的治疗策略可选择新辅助化疗、乳腺癌改良根治术、保乳+腋窝清扫术、腋窝清扫术;乳腺病理学未检出原发灶的患者复发转移率低于检出原发灶者。     

Fecal DNA-based detection of colorectal neoplasia

Human DNA fragments, as well as whole colonocytes, can be found in stool and interrogated for mutations associated with carcinogenesis. Multiplexed panels of point mutations in fecal DNA improved the sensitivity of cancer detection (51.6%; 95% CI, 34.8%–68%) compared with fecal occult blood testing (12.9%; 95% CI, 5.1–28.9). However, the multiplex panels are not more sensitive than fecal occult blood testing in detecting advanced adenomas. Markers of epigenetic events, such as DNA methylation of gene promoters in genes not previously known to be associated with carcinogenesis or colorectal cancer, have recently been shown to be potential markers for early detection. Future approaches to improve sensitivity of fecal DNA detection of colorectal adenocarcinoma may require the inclusion of epigenetic biomarkers, the use of colonocytes isolated from feces, or both.     

Impact on survival of early detection of isolated breast recurrences after the primary treatment for breast cancer: a meta-analysis

Purpose The purpose was to establish the impact on survival of early detection of a local recurrence of breast cancer as compared to late detection. Design A meta-analysis was carried out using Cochrane review manager software (RevMan version 4.2). Studies were included if women were treated for primary breast cancer without evidence of distant metastasis at primary diagnosis and if these concerned routine follow-up strategies focusing on the early detection of curable recurrences. Data regarding the risk for death were derived from each study. Multi level models were used to study heterogeneity by using MLWin. Results Thirteen studies concerning 2,263 patients were included. Early detection of breast cancer recurrences during follow-up gave a significantly better survival as compared to late detected recurrences (HR: 1.68 (95% CI: 1.48–1.91)). Survival was better when the recurrence was found by mammography instead of physical examination or in patients without symptoms as compared to those with symptoms (HR: 2.44 (95% CI: 1.78–3.35); HR: 1.56 (95% CI: 1.36–1.79), respectively). If all breast cancer recurrences would be detected earlier, that 5–8 deaths (i.e. an absolute reduction in mortality of 17–28%) would be avoided by performing routine follow-up during a 10 year-period for 1,000 breast cancer patients. Conclusion These data support the hypothesis that detection of isolated loco-regional or contra-lateral breast cancer recurrences in patients without symptoms has beneficial impact on survival of breast cancer patients when compared to late symptomatic detection.     

Prognostic significance of occult axillary lymph node metastases after chemotherapy‐induced pathologic complete response of cytologically proven axillary lymph node metastases from breast cancer

BACKGROUND:

Primary systemic chemotherapy has been a standard of care for the management of locally advanced breast cancer (LABC) patients and has increasingly been used for patients with large operable breast cancer. Pathologic complete response (pCR) of axillary lymph node metastases predicted an excellent probability of long‐term disease‐free and overall survival. Although the clinical significance of occult lymph node metastases in patients with breast cancer was extensively studied, their prognostic value in patients with LABC after primary chemotherapy was not known. This study evaluated the detection rate and clinical significance of occult lymph node metastases in lymph nodes that contained metastatic carcinoma at the time of initial diagnosis and converted to negative based on routine pathologic examination after primary systemic chemotherapy.

METHODS:

Fifty‐one patients with LABC and cytologically involved axillary lymph nodes that converted to negative after preoperative chemotherapy were identified from 2 prospective clinical trials. All lymph node sections were reviewed, 1 deeper level hematoxylin and eosin‐stained section of each lymph node was obtained and immunohistochemical staining for cytokeratin (CK) was performed. A total of 762 lymph nodes were evaluated for occult metastases. Kaplan‐Meier survival curves were used for calculating disease‐free and overall survival times.

RESULTS:

Occult axillary lymph node metastases were identified in 8 of 51 (16%) patients. In 6 patients, occult metastases were found in only 1 lymph node. In 7 patients, only isolated CK‐positive cells were identified. In all cases, occult carcinoma cells were embedded within areas of fibrosis, foreign body giant cell reaction, and extensive histiocytosis. Patients with occult lymph node metastases tended to have a higher frequency of residual primary breast tumors than those without occult metastases (4 of 8 vs 7 of 43, respectively). There was no statistically significant difference in disease‐free or overall survival times between patients with and without occult metastases after a median follow‐up 63 months.

CONCLUSIONS:

Persistent occult axillary lymph node metastases were not uncommon in patients with axillary lymph node‐positive LABC who experienced a pCR in involved lymph nodes after preoperative chemotherapy. However, such occult metastases did not adversely affect the good prognosis associated with axillary lymph node pCR. Therefore, routine lymph node CK evaluation was not recommended after primary chemotherapy. Cancer 2009. © 2009 American Cancer Society.     

隐性乳腺癌的诊治(附68例报告)

目的：探讨隐性乳腺癌的发病特点、检诊规范和治疗方法.方法：回顾性分析68例隐性乳腺癌临床病理资料和治疗效果.结果：全组均经腋窝淋巴结活检及免疫组化M4G33检测明确诊断,65例行根治术或改良根治术,3例行腋窝肿块切除,术后全部辅助放、化疗,全组5、10年生存率分别为77.9%和58.12%;术后常规病检原发灶检出率33.8%（22/65）,结合全乳腺次连续大切片检查,病理原发灶总检出率达86.2%（56/65）.结论：对女性腋窝肿块同时排除全身其它部位癌转移者应高度考虑隐性乳腺癌,腋窝淋巴结活检和免疫组化M4G3检测对确诊有重要意义;根治术标本宜行全乳腺次连续大切片检查以提高原发癌灶检出率,治疗宜选择根治术或改良根治术并辅助放疗、化疗以及内分泌治疗.     

Malignant neoplasm in the axilla of a male: suspected primary carcinoma of an accessory mammary gland

A 58-year-old Japanese male patient visited our hospital for evaluation of an elastic hard mass, measuring 80 × 50 mm, in the right axillary area. Incisional biopsy for suspected malignancy was performed, and histopathologic examination by hematoxylin–eosin (H&E) staining yielded a diagnosis of poorly differentiated adenocarcinoma metastatic from an unknown primary. As the tumor was immunohistochemically positive for both ER and PgR, metastatic breast cancer was strongly suspected. Ultrasonography, CT, and MRI revealed no evidence of tumors in the bilateral mammary glands. Detailed examination of the head and neck region, lung, and upper and lower gastrointestinal tract also revealed no evidence of a primary tumor. After chemotherapy, the patient underwent tumor resection with axillary lymph node dissection. On the basis of the histological features of H&E-stained specimens and immunohistochemistry of the resected tumor, this case was diagnosed as breast cancer of unknown origin in a male. The tumor could have been an axillary lymph node metastasis from an occult breast carcinoma, or primary cancer arising in an accessory mammary gland.     

Rectal metastasis from lobular breast carcinoma 15 years after primary diagnosis

Lobular breast carcinoma represents 2–20% of infiltrative carcinomas of the breast. The incidence of extrahepatic gastrointestinal (GI) tract metastases observed in necropsy studies varies from 6% to 18% and the most commonly affected organ is the stomach, followed by colon and rectum [1–4]. Reported herein is the case of a 67-year-old woman who was primarily diagnosed and surgically treated for a lobular carcinoma of the breast 15 years ago and is now referred with back pain and right hydronephrosis caused by a metastasis in rectum. Frequently, the absence of specific symptoms of digestive metastases of breast cancer leads to a misdiagnosis of this pathology [5–7]. The treatment will be based on a detailed clinical history and histopathological findings. Metastases from breast cancer in GI tract tumours must be excluded in a patient with previous history of breast carcinoma, as in the case reported herein.     

隐匿性乳腺癌36例诊治分析

回顾分析临沂市肿瘤医院乳腺外科收治的36例隐匿性乳腺癌(OBC)患者的临床资料,并结合文献进行讨论。所有病例腋下肿物均经切检病理确诊。乳腺钼靶检查2例诊断为乳腺癌,3例患者为可疑乳腺癌;乳房彩超检查1例诊为乳腺癌,3例患者为可疑乳腺癌。行改良根治术28例,乳腺癌根治术4例,保留乳房手术2例,腋窝淋巴结清除加全乳放疗2例。30例患者获得随访,15例生存时间>5年。回顾分析结果提示,对腋下肿块应行切除活检以明确诊断;乳腺钼靶、彩超及腋下肿物激素受体检测有一定价值;乳腺核磁共振扫描能够提高OBC的检出率。手术方式宜采用改良根治术或保留乳房后全乳照射,并辅以化疗及内分泌治疗等以提高长期生存率。     

Predictors of local recurrence after conservative surgery and whole-breast irradiation

Purpose To identify independent factors associated with increased risk of local recurrence (LR) in patients with breast cancer treated with conservative surgery and radiotherapy with or without systemic therapy.Methods and materials Between January 1997 and December 2001, 969 women were treated at the Radiation Oncology Department in Chieti. We retrospectively analyzed 802 of them who were treated with conservative surgery and whole breast irradiation with or without systemic therapy. Tangential fields delivering 50 Gy to the whole breast were used and a boost was added for a total dose of 60 Gy. χ²-test or Fisher’s exact test were used to identify independent significant factors that are predictive for LR. Kaplan–Meier method was used to calculate the 8-year rates of recurrence according to age, histologic findings, tumor size, number of positive nodes, margin status, receptor status and systemic therapy use: log-rank test was used to compare these curves. Cox proportional hazard model was used to obtain hazard ratios and 95% CI of LR for each covariate.Results Median follow-up time was 63.1 months. LR occurred in 33 (4.1%) of 802 patients. Percentage of LR was greater in <50 year-olds compared with 50–64 year-olds and ≥65 year-olds (9.8% versus 4.1 and 2.0%, respectively). LR was 18.8% in women with a tumor size >3 cm versus 3.5, 4.0, 5.5% in women with a tumor size of 0.1–1, 1.1–2, 2.1–3 cm, respectively. The 8-year LR rate calculated with Kaplan–Meier method was 6.54±1.51. Multivariate Cox regression analysis showed that independent significant factors that are predictive for LR were: age <50, tumor size >3 cm, positive margin or unknown status, and hormonal therapy alone versus chemotherapy or combined therapy.Conclusions Age and tumor size were the most important and statistically significant factors that correlated independently with higher rates of LR. Women <50 years old and with a tumor size >3 cm had a higher risk of LR. Also margin status and systemic therapy could influence LR risk.     

Family history of malignancies and risk of breast cancer: prospective data from the Shanghai women’s health study

A population-based cohort study was conducted in Shanghai, China, to investigate the relationship between family cancer history in first-degree relatives and risk of breast cancer. A total of 570 newly diagnosed breast cancer patients were identified from the cohort of 73,222 women during the follow-up period. Breast cancer risk was elevated (RR = 1.74, 95% CI: 1.10–2.73) for those with a family history of breast cancer and the risk was stronger for women who were younger than 55 years (RR = 2.07, 95% CI: 1.17–3.64). In addition, a significantly increased risk was observed for women with a family history of leukemia (RR = 2.06; 95% CI: 1.02–4.15) and among younger women, those who reported having a family history of any cancer (RR = 1.41, 95% CI: 1.10–1.82), lung cancer (RR = 1.72, 95% CI: 1.12–2.65), and esophageal cancer (RR = 2.99, 95% CI: 1.62–5.51). This cohort study suggests that, as previously observed in high risk populations, family history plays an important role in breast cancer also in a low risk population. The link between breast cancer risk and family history of cancers of the lung and esophagus, as well as leukemia, warrants further investigation.     

乳腺微小钙化灶的定位切除和病理活检

 目的　介绍乳腺内触诊阴性的微小钙化灶定位切除与活检的方法 ,为定性诊断提供组织学依据 ,提高临床触诊阴性乳腺癌的早诊率。方法　 10 2例共 111侧乳腺微小钙化灶均在X线下放置 1～ 2根金属定位线 ,在定位线引导下行钙化灶切除及病理组织学检查。结果　全组乳腺癌 2 6例 ,占 2 5 .5 % ,钼靶片显示乳腺实质内的针尖样或沙粒样钙化灶 ,密度均匀一致 ,颜色深浅适中 ,多点成簇 ;乳腺良性疾病 76例 ,占 74 .5 % ;钼靶片显示乳腺实质和间质中的小点状和 /或小杆状钙化灶 ,大小不一 ,密度不均 ,数目少且散在。术前决定切除的钙化灶均一次性完整切除 ,无 1例再行补切 ,无并发症。结论　在影像科、外科、病理科的合作下 ,利用金属线在X线引导下对乳腺内微小钙化灶定位 ,在定位线引导下行钙化灶切除及病理组织学检查是一种有效而安全的诊断方法 ,提高了无肿块乳腺癌的早诊率 ;此方法简单易行便于推广。     

1例转移性隐匿性乳腺癌的临床诊治

隐匿性乳腺癌(occult breast cancer, OBC), 是较少见的特殊类型乳腺癌, 指经临床体检和影像学检查未发现乳房内包块而以腋窝淋巴结转移或其他远处转移为首发症状, 并经病理证实来源于乳腺组织的乳腺癌。对转移淋巴结进行组织病理学检查是OBC诊断的关键。对于钼靶和超声阴性的OBC, 增强核磁共振(MRI)检查在寻找原发灶方面有重要作用, 且有助于OBC的术前定位和指导手术方案。其手术治疗方法的选择尚有争议。现介绍1例晚期转移性OBC, 经多学科联合诊治、予以个体化综合治疗的成功经验, 为OBC的诊治提供更多思路, 强调多学科协作诊疗模式。      

The clinical significance of 99mTc-MIBI breast imaging in the diagnosis of early breast cancer

Objective: To find an effective, sensitive, specific and noninvasive diagnostic method of breast cancer. Methods: 109 masses of 102 patients with breast lesions smaller than 2 cm in diameter were divided into three groups to undergo ^99mTc-MIBI imaging and compared with the results of pathology examination. 20 cases without breast lesions were selected as control. Abnormal condensation of ^99mTc-MIBI in the breast reaching 10% higher than that in the counterpart of the healthy breast was regarded as positive. Results: Of 32 breast cancers, positive imaging appeared in 25. Negative imaging were found in 31 of 38 benign breast lesions. Of 39 occult breast lesions, positive imaging appeared in 6 and 3 of them were breast cancer, 2 of 3 patients with slightly increased ^99mTc-MIBI imaging threshold were breast cancer also. No positive imaging was found in the control group. The diagnostic accuracy, sensitivity, specificity, positive predictive value, negative predictive value of ^99mTc-MIBI was 88.4%, 89.2%, 88.0%, 75.0% and 95.3%, respectively. Conclusion: ^99mTc-MIBI imaging had higher sensitivity and accuracy in the diagnosis of breast cancer and differentiation between benign and malignant breast lesions. It could provide useful information for the diagnosis of clinically suspected breast cancer. Biography: Ren Chang-cai, (1951–), associate professor of general surgery, majors in breast and thyroid diseases, especially skillful on diagnosis and treatment of early stage breast cancer and treatment of advanced breast cancer.     

An extraordinary case in whom gastrointestinal stromal tumor and low-grade malignant lymphoma are seen together in the stomach

Introduction Gastrointestinal system (GIS) is the most common site of involvement of all primary extranodal lymphomas. Gastric lymphoma constitutes 3–6% of all primary stomach malignancies. Stomach is also the commonest site of involvement of gastrointestinal stromal tumors (GIST). We would like to report these rare synchronous tumors in the same patient. Case A 68-year-old male was admitted to the internal medicine clinics with the complaints of abdominal distension. Physical examination was normal. On abdominal computed tomography a 12 × 14 × 22 cm sized giant tumoral mass was detected in left hypochondrium. A total gastrectomy was performed. Two distinct neoplasms were detected; one of which was located in the posterior wall of the stomach with the size of 24 × 16 × 13 cm, and the other one was localized in the fundus of the stomach and its size was 6 × 5 × 2 cm. Pathological evaluation revealed the diagnosis of GIST at the posterior wall and low-grade malignant lymphoma from the mass localized in the fundus of the stomach. Discussion Two primary tumors are not seen so often together in the stomach. Adenocarcinoma and associated tumors including gastric lymphoma (especially MALT lymphoma), carcinoid, leiomyosarcoma and rhabdomyosarcoma constitute most of the reported series. Rarely adenocarcinoma and associated GIST cases were reported. It is important to report concurrent gastric lymphoma and GIST case since it is extremely rare in the English literature.