Occult breast carcinoma presenting as axillary metastases

PURPOSE: Breast carcinoma presenting with axillary lymphadenopathy and no clinical or radiological evidence of a primary tumor is a rare presentation. We aimed to examine the management of the breast by observation, radiation therapy, or mastectomy. METHODS AND MATERIALS: Departmental records from 1979 to 1996 of unknown primary presentations and cases of T0N1-2M0 breast carcinoma were reviewed to find cases of occult breast carcinoma presenting as axillary lymphadenopathy with no clinical or imaging evidence of a primary tumor. RESULTS: There were 6047 presentations of breast carcinoma with 20 cases of occult breast carcinoma meeting the criteria. The breast was treated by observation in 6 cases, mastectomy in 2 cases, and radiotherapy to the intact breast in 12 cases. Eighty-three percent of patients (5 of 6 patients) who had observation of the breast had a local recurrence, compared to 25% who had radiotherapy to the intact breast (3 of 12 patients) and 0% who had a mastectomy (0 of 2 patients). The median recurrence-free survival was 7 months in patients who had observation of the breast, compared to 182 months in patients who had local treatment. Three of the 6 patients who underwent breast observation have died whereas 1 of the 14 who had local treatment have died, with a mean follow-up of 73 months. It was found that patients having observation of the breast had a poorer recurrence-free survival (p = 0.003) and overall survival (p = 0.05) compared to those having local treatment of the breast. CONCLUSIONS: Patients with such a presentation should have a complete physical examination, mammography, ultrasound, and MRI of the breasts. If there remains no evidence of a primary tumor, an axillary dissection should be carried out and the breast treated by radiotherapy or mastectomy. Observation of the breast is not a recommended option.     

Occult breast carcinoma — Use of color Doppler in localization

Summary Occult breast carcinoma presenting with axillary metastases is a difficult clinical problem. Mammography is recommended as the diagnostic tool for detecting breast masses, but is very insensitive. In two consecutive patients with nonpalpable carcinoma of the breast, the detection of breast lesions was made by color Doppler sonography. The sensitivity of the technique makes it a useful diagnostic aid in patients with negative mammograms.     

Incidence of breast carcinoma in women with thyroid carcinoma

BACKGROUND: Breast carcinoma and differentiated thyroid carcinoma(the most common endocrine malignancy) occur predominantly in women. An association between the two tumors has been suggested by some investigators, but the potential impact of treatment of one of these diseases on the development of the other remains unclear. The authors examined the relation between the occurrence of these two tumors. METHODS: There were 41,686 patients with breast carcinoma and 3662 with thyroid carcinoma who registered at The University of Texas M. D. Anderson Cancer Center between March 1944 and April 1997. Women who received both diagnoses since 1976 were identified and incidence rates and relative risks of secondary tumor development were calculated. Surveillance, Epidemiology and End Results (SEER) program data on the age-adjusted incidences of these diseases during the same time period were used for the expected incidences in the same population. RESULTS: Among 18,931 women with a diagnosis of breast carcinoma since 1976, 11 developed differentiated thyroid carcinoma > or = 2 years after the diagnosis of breast carcinoma. These breast carcinoma patients contributed 129,336 person-years of follow-up; the observed incidence of thyroid carcinoma in this group was not different from that in a similar age group of women in the SEER database. Among 1013 women with a diagnosis of thyroid carcinoma since 1976, 24 developed breast carcinoma > or = 2 years after the diagnosis of thyroid carcinoma. These thyroid carcinoma patients contributed 8380 person-years of follow-up; the observed incidence of breast carcinoma in women ages 40-49 years was significantly higher than the expected incidence for women in the same age group in the SEER database. CONCLUSIONS: Breast carcinoma developing after thyroid carcinoma was diagnosed more frequently than expected in young adult women seen at the study institution since 1976. This potential association and plausible mechanisms of breast carcinoma development after thyroid carcinoma should be evaluated in larger cohorts of patients.     

The development of breast carcinoma in women with thyroid carcinoma

BACKGROUND: Breast carcinoma and thyroid carcinoma are two malignancies that occur most commonly in women. An association between the incidence rates of thyroid and breast carcinoma in women after a diagnosis of the other malignancy has been suggested in a retrospective analysis of a single institution's tumor registry. In that study, an increased incidence of breast carcinoma in premenopausal women previously treated for thyroid carcinoma was observed. METHODS: The purpose of this study was to investigate further this relation utilizing a large database, the National Cancer Institute's Surveillance, Epidemiology and End Results (SEER) database. The SEER database is maintained by the National Cancer Institute, and it represents 11 population-based cancer registries covering approximately 14% of the United States population. The study was a population-based retrospective cohort analysis using external comparisons. From 1973 to 1994, 365 women in the SEER database were identified as having both thyroid and breast carcinomas. The SEER database from 1973 to 1994 was utilized to calculate age specific and calendar year specific incidence rates for each year for thyroid and breast carcinomas. The expected number of second cancers for each age group, calendar year, and follow-up period were determined by multiplying these incidence rates by the age specific and calendar year specific number of person-years at risk. The risk ratio (RR) was calculated by dividing the observed by the expected number of second cancers. Statistical significance was determined by the Poisson test. RESULTS: A total of 1,333,115 person-years were available for analysis. One hundred thirteen thyroid carcinoma cases were diagnosed after breast carcinoma cases (RR, 0.99; P = 0.576). Two hundred fifty-two breast carcinoma cases were diagnosed after thyroid carcinoma cases (RR, 1.18; P = 0.007). Premenopausal women (age 20-49 years) with an index thyroid carcinoma have a significantly increased risk of developing subsequent breast carcinoma (RR, 1.42; P = 0.001). Black premenopausal women with an index thyroid carcinoma do not have an increased risk of developing breast carcinoma, but the statistical power is lower due to low numbers. No women with index breast carcinoma have an increased risk of developing thyroid carcinoma. CONCLUSIONS: Women with a history of thyroid carcinoma have a greater than expected risk of developing breast carcinoma. This risk is most pronounced in premenopausal white women. The implications of this observation with respect to breast carcinoma screening guidelines and thyroid carcinoma treatment guidelines deserve further investigation.     

DNA repair and breast carcinoma susceptibility in women

BACKGROUND: Breast carcinoma is the most common cancer and the second leading cause of cancer-related deaths among women. The disease represents approximately 31% of all cancers in Puerto Rican women. Several DNA repair pathways are involved in preventing carcinogenesis. The current study evaluated the hypothesis that a reduced DNA repair capacity (DRC) is a susceptibility factor for breast carcinoma. METHODS: A retrospective case-control clinical study was performed to compare age-matched DRC in 33 women with histopathologically confirmed breast carcinoma (cases) and 47 cancer-free women (controls). DRC was measured using a host cell reactivation assay with a luciferase reporter gene and then transfected into human peripheral lymphocytes. A questionnaire was used to solicit breast carcinoma risk factors. RESULTS: Women with breast carcinoma had a mean DRC of 5.6% +/- 0.5 standard error of the mean (SEM). Cancer cases had a 36% reduction (P<0.001) in DRC when compared with the control group (DRC=8.7% +/- 0.7 SEM). Younger participants with breast carcinoma were found to have a more significant reduction in DRC when compared with age-matched controls. Family (odds ratio [OR]=4.1), maternal lineage (OR=5.5), and maternal (OR=12.4) history of breast carcinoma were found to be the only statistically significant (P<0.05) risk factors associated with the disease. CONCLUSIONS: The findings supported the hypothesis that a low DRC is a susceptibility factor for breast carcinoma. A 1% decrease in DRC corresponded to a 22% increase in breast carcinoma risk. To the authors' knowledge, the current study was the first to directly determine the DRC of women with breast carcinoma. Because DRC is an independent risk factor for breast carcinoma, the DRC of women may be a useful marker in predicting susceptibility.     

Discrepancy in ER levels of breast carcinoma in biopsy vs mastectomy specimens

The presence of estrogen receptors (ER) in breast tumors has been used by many as the major indicator for hormonal treatment of breast cancer. However, multiple factors have been shown to be involved in determining the hormone dependence of breast cancer. This paper reports another factor that influences the accuracy of ER determination. From January 1977 through December 1983 fifty-eight (58) of these patients had ER determination of both biopsy and mastectomy specimens. Of the 31 patients that remained ER positive in mastectomy specimen, 13 had significantly lower ER levels (by at least 50%) from the mastectomy specimens. These findings indicate that ER status is greatly influenced by the source of the specimen.     

Contralateral cancerous breast lesions in women with clinical invasive breast carcinoma

Eighty-four consecutive autopsies of women with a clinical diagnosis of invasive breast carcinoma (BC) were examined by extensive histopathologic methods for malignant changes of the contralateral breast. Sixty-eight percent of the women were found to have primary contralateral BC, of which 33% were invasive and 35% in situ lesions. Another 16% had metastases to the breast. Only two women had had treatment for their contralateral BC. In eight cases a malignant lesion was diagnosed or suspected clinically, but in the remaining cases, the malignancies were identified only by histopathologic examination. No clinical data or histologic characteristics of the first BC had any predictive value for the risk of contralateral BC. In the contralateral breast, a significant coincidence was found between fibrocystic disease and the occurrence of primary malignant BC. The majority of the BC on both sides were of ductal type. Seventy-nine percent of the invasive contralateral BC were tumefacient, and 71% had axillary lymph node metastases. The mean survival time was comparable for women with and without contralateral primaries, but a significantly higher proportion of women with contralateral invasive BC died of disseminated BC. The frequency of contralateral malignancies is thus much higher than previously reported. The consequence of these findings may implicate a reevaluation of the treatment and control schedule regarding the contralateral breast in women with invasive BC.     

Occult breast carcinoma: a report of four cases and review of literature

We report four occult carcinoma breast cases in which extensive axillary node metastases was the first manifestation. Upper outer quadrentectomy with axillary dissection was done in three patients while modified radical mastectomy was done in one. Primary tumor could be found in three patients, one had squamous cell carcinoma (SCC) & two had infiltrating duct carcinoma (IDC). However primary tumor was not detected in breast tissue of the fourth patient. Extensive lymph node metastases were found in three out of 14,15 out of 15(SCC), 24 out of 24 and 1 out of three axillary nodes respectively. Results of immunohistochemical staining for estrogen and progesterone receptors on three cases were negative. All patient received postoperative radiotherapy and chemotherapy. We have reviewed the literature and discussed the approach to diagnosis and management in female patients presenting with metastatic carcinoma in the axillary nodes with emphasis on the appropriate pre-treatment evaluation.     

Identification of distinct protein expression patterns in bilateral matched pair breast ductal fluid specimens from women with unilateral invasive breast carcinoma. High-throughput biomarker discovery

BACKGROUND: Analysis of the biochemical and cellular contents of breast ductal fluid has recently gained attention as a potential noninvasive method for studying the local microenvironment associated with the development and progression of breast carcinoma. METHODS: Patients with unilateral primary invasive breast carcinoma were eligible for the current prospective pilot study. Nipple aspiration fluid (NAF) was obtained from the breast with cancer and the normal contralateral breast and subjected to two-dimensional electrophoresis. Computer-assisted image analysis was used to analyze NAF protein expression profiles. RESULTS: The number of separate protein spots detected in NAF samples ranged from 1280 to 1649. Substantial qualitative differences were identified between NAF protein expression patterns in the breast with cancer compared with the breast without cancer. Protein spots detected in the breast with cancer and not in the breast without cancer from the same patient varied from 30 to 202 different proteins. In addition, the number of protein spots detected in the breast without cancer and not in the breast with cancer of the same patient varied from 14 to 73 different proteins. Conversely, in an individual without breast carcinoma, only three protein spots were detected in the left breast but not the right breast, and only two were detected in the right breast but not the left breast. CONCLUSIONS: The breast is a unique organ in that its microenvironment can be readily accessed and evaluated by aspiration of fluid from the nipple. Breast ductal fluid contains a large number of proteins. As breasts are paired organs, comparisons of ductal fluid from a breast with cancer and the same patient's normal contralateral breast may reveal significant differences in protein expression associated with breast carcinoma. Recent advances in image analysis, automated mass spectrometry, and bioinformatics have provided the tools necessary to use ductal fluids from breast carcinoma patients for high-throughput biomarker discovery.     

A problem-solving approach to stress reduction among younger women with breast carcinoma: a randomized controlled trial

BACKGROUND: Previous research indicates that younger women (i.e., 50) and that coping style is significantly related to the psychosocial adjustment of women with this disease. The purpose of this study was to evaluate through a randomized controlled trial the effectiveness of a problem-solving training intervention designed to empower women with breast carcinoma to cope with a range of difficulties when diagnosed in mid-life. METHODS: The study population consisted of women aged 50 years or younger who had no prior history of breast carcinoma, were diagnosed with Stage I-IIIA tumors, and for whom a first course of chemotherapy had been initiated recently. The intervention consisted of two in-person and four telephone sessions with an oncology nurse who provided problem-solving skills training and informational materials to the women over a 12-week period. All subjects were assessed for physical and psychosocial adjustment through telephone and mailed surveys at baseline, at 4 -months, and at 8 months. RESULTS: Of 183 eligible women, 164 participated (a 90% participation rate), 149 of whom completed the study (a 91% completion rate). The subjects had significantly lower unmet needs and better mental health at the 4-month assessment. The intervention significantly decreased the number and severity of difficulties experienced by women with average or good problem-solving skills at 8 months, but was not effective in alleviating or resolving the problems encountered by women with poor problem-solving skills, relative to the control group. CONCLUSIONS: We conclude that this problem-solving therapy-based home care training intervention is an effective method of helping the majority of women with breast carcinoma to reduce the stresses associated with the diagnosis and treatment of cancer in mid-life.     

Autoimmune thyroid disease in women with breast carcinoma.

AIMS: Estimation of prevalence of autoimmune thyroid disorders in Greek breast cancer patients (prospective study). METHODS: The prevalence of autoimmune thyroiditis was estimated in 310 Greek breast cancer patients, in 100 women with benign breast disease and in 190 women without any breast disease, by submitting them to clinical examination, ultrasound thyroid evaluation, serum thyroid antibody determination and fine needle aspiration (FNA) of the thyroid gland. RESULTS: Autoimmune thyroiditis was found in 136/310 (43.9%) breast cancer women: 95 were diagnosed by positive autoantibodies, 19 had positive FNA findings and 22 had both positive autoantibodies and positive FNA findings. In 117 cases, thyroid autoantibodies were positive (37.7% whereas the control groups had respective rates of 19% and 18.4% autoantibody positivity). CONCLUSIONS: There is evidence of high incidence of autoimmune thyroiditis in Greek breast cancer patients, increasing in relation to cancer stage.     

The association between breast carcinoma and meningioma in women

BACKGROUND: Published case reports of a possible association between meningioma and breast carcinoma are not uncommon in the literature. Four published analytic studies have addressed this suggested association specifically. Three of these studies reported significant associations, with relative risk estimates mostly between 1.5 and 2.0. The other study reported relative risk point estimates near 1.5, but confidence intervals included 1.0. The current study was a population-based, retrospective cohort analysis that evaluated the risk of subsequent breast carcinoma in women who were diagnosed with meningioma and the risk of subsequent meningioma in women who were diagnosed with breast carcinoma. METHODS: The measure of association is the relative risk and is reported as the standardized incidence ratio (SIR). Using western Washington State cancer registry data and intercensal population estimates for western Washington State, incidence rates of second primary tumor were compared between identified meningioma and breast carcinoma cohorts and the general population for the years 1992-1998. RESULTS: The risk of breast carcinoma after patients were diagnosed with meningioma (SIR) was 1.54 (95% confidence interval [95% CI], 0.77-2.75). The risk of meningioma after patients were diagnosed with breast carcinoma was 1.40 (95% CI, 0.67-2.58), and the risk of meningioma after patients were diagnosed with invasive breast carcinoma was 1.64 (95% CI, 0.79-3.02). In each combination for age groups ages > 50 years, risks were elevated, but the confidence intervals included 1.0. CONCLUSIONS: These results suggest that the risk of meningioma among women who have experienced breast carcinoma and the risk of breast carcinoma among women who have experienced meningioma are elevated moderately. Shared risk factors may account for the relatively week bidirectional associations seen in this and other studies.     

Childbearing and survival after breast carcinoma in young women

BACKGROUND: Many young patients with breast carcinoma have not started, or completed, their desired families. How childbearing after a diagnosis of breast carcinoma affects survival is of importance to these women and their families. The authors measured relative mortality among young patients with breast carcinoma with and without births occurring after diagnosis. METHODS: The authors conducted a cohort study using data from three population-based cancer registries in the U.S. (Seattle, Detroit, and Los Angeles), linked to birth certificate data in each state. Four hundred thirty-eight women younger than 45 years of age with primary invasive breast carcinoma were identified as having births after diagnosis. In addition, 2775 comparison women, matched on the basis of age at the time of diagnosis, race/ethnicity, diagnosis year, disease stage, and presence of previous nonbreast primary tumors, were identified among those with breast carcinoma without births after diagnosis. Relative mortality was assessed using multivariable statistical methods. RESULTS: After adjustment for stage of disease, age at diagnosis, study region, diagnosis year, and race/ethnicity, women with births occurring 10 months or more after diagnosis had a significantly decreased risk of dying (relative Risk [RR] = 0.54, 95% confidence interval [CI], 0.41-0.71) compared to women without subsequent births. Women pregnant at the time of diagnosis had a mortality rate similar to those who did not give birth (RR = 1.10, 95% CI, 0.80-1.60). CONCLUSIONS: The results of the current study, in light of growing evidence from other studies using various methods, may provide some reassurance to young women with breast carcinoma that subsequent childbearing is unlikely to increase their risk of mortality.     

Estrogen and progesterone receptor assays on breast carcinoma from mastectomy specimens

Two patients, 60 and 62 years old, were admitted with progressive dysphagia and weight loss of 8 to 12 weeks duration. Radiographic studies revealed an area of stenosis in the lower third of the esophagus in both cases. Endoscopic and biopsy findings established the diagnosis of a neoplasm, with malignant signet ring cells infiltrating the mucosa. Partial esophagogastrectomy in both cases disclosed an infiltrative adenocarcinoma of the lower esophagus, without involvement of the gastroesophageal junction. One of the patients had metastases to regional lymph nodes; the other patient has no clinical evidence of recurrence 14 months after surgery. Endoscopic, radiologic, and pathologic findings are consistent with the diagnosis of linitis plastica of the esophagus.     

Occult breast carcinoma presenting with axillary lymph node metastases: follow-up of eleven patients

BACKGROUND: Breast carcinoma presenting with axillary metastases and no clinically apparent primary tumor in the breast is an uncommon form of stage IIdisease. The methods of diagnosis and treatment of these patients are not established. We present our eleven treated cases of occult carcinoma and discuss the issues of evaluation and management. METHODS: Eleven patients with occult breast carcinoma (OBC) presenting between January, 1985 and April, 1998 at the National Shikoku Cancer Center were evaluated clinically and with immunohistochemical staining. Immunohistochemical staining was performed using the Envision method. The primary antibodies for gross cystic disease fluid protein-15 (GCDFP-15), estrogen receptor (ER) and progesterone receptor (PR) were used. RESULTS: Nine patients underwent mastectomy. Breast-conserving surgery was performed in one patient. One patient did not receive any operation for the breast. No primary tumor was found among three of nine cases receiving mastectomy. Some adjuvant therapies after the operation were performed in eight cases. Follow-up ranged from 5 to 310 months (median, 54 months), and the five-year disease free survival rate was 62.5%. There were eight GCDFP-15 positive cases (72.7%) and four ER and/or PR positive cases (36.4%). CONCLUSIONS: GCDFP-15 is useful for confirming the primary site of breast carcinoma. Ultrasonography, computed tomography, and magnetic resonance imaging are thought to be good for detecting occult primary tumors. The incidence of OBC is still unclear, but it is possible that these patients need to be treated as typical stage II patients.     

Occult breast cancer and axillary mass

Opinion statement Occult breast cancer presenting with axillary metastases is an unusual presentation and can be a diagnostic and therapeutic challenge. A comprehensive work-up, including mammogram, sonogram, magnetic resonance imaging, and even pathologic examination of the mastectomy specimen may not disclose the primary tumor in up to one third of patients. Traditionally, occult breast cancer is treated with total mastectomy and axillary dissection, but accumulating data suggest that primary breast irradiation following axillary dissection may provide an equivalent survival with the advantage of breast conservation. Occult breast cancer patients are eligible for adjuvant chemotherapy and radiation as stage II/III node-positive patients would be treated. Overall, the prognosis for occult breast cancer is equivalent to or slightly better than staged counterparts with detectable primary breast tumors.