Bilateral Primary Breast Cancer Research Articles

BRCA1/2 mutations as prognostic factors in bilateral breast cancer (BC) patients

9647 Background: Incidence of primary bilateral BC is rare and not extending 5%. BRCA1/2 mutation carriers diagnosed with BC have a strong life time risk of developing a contralateral BC (53% vs 2%). Methods: We analyzed the group of 108 patients with bilateral BC who attended our Cancer Center between 2000 and 2002 and who gave their consent for genetic test. Patients with synchronous BC were defined as having contralateral BC within 1 year. Similarities and differences between BRCA1/2 carriers and non carriers were analyzed in terms of family history, pathology of tumor, age of diagnosis and development of contralateral BC and second cancer. Results: The median age of the group at the time of diagnosis of BC was 47 years (28–76). Before age of 50, BC developed 73% of patients, including 22% before age of 40. Synchronous BC was diagnosed in 30 (28%) patients, metachronous in 78 (72%). Family history of BC was present in 32/108 patients, and of ovarian cancer in 5/108 patients. BRCA1/2 mutation was detected in 32/108 patients. Family history of BC was identified in 46,9% of these patients, comparing to 22,4% of non carriers (p<0.05). Synchronous BC was diagnosed significantly rarer 4/32 (12.5%) in BRCA1/2 carriers than in non carriers group 26/76 (34.2%). Also patients with BRCA mutations when diagnosed were younger than non carriers (41.3 vs 47.9) and time to diagnosis of contralateral BC was shorter. BRCA1/2 carriers had significantly higher incidence of medullary BC (13.6% vs 1.7%). There was no difference in the incidence of other tumor pathology. BRCA1/2 carriers developed significantly more frequent ovarian cancer than non carriers 12/32 and 1/72 respectively. Conclusions: Patients with bilateral BC having BRCA mutations are significantly younger, than non carriers and time of developing of contralateral BC is shorter.They have significantly more frequent family history of BC and higher risk of developing of ovarian cancer. The differences in clinical aspects of BRCA carriers with bilateral BC, should be considered in clinical management. No significant financial relationships to disclose.

CLINICOPATHOLOGICAL STUDY OF PRIMARY BILATERAL BREAST CANCER

In a series of 709 patients with breast cancer operated on at the department in a recent three decades from 1968 to 1998, there were 33(4.7%) patients with primary bilateral breast cancer. Eleven patients(1.6%) had synchronous and 22 patients(3.1%) had metachronous bilateral breast cancers. These 33 patients were clinicopathologically compared with those having unilateral breast cancer. Average age at operation for the first cancer in metachronous patients was 42.9 years, that was significant younger than others. Patients with bilateral breast cancer had history of familial cancer or other multiple primary cancers in a high frequency. In metachronous patients 80% of them found the second cancer by themselves, which 27% of synchronous patients found it by themselves, with a significant difference. The 5-year survival rates were 86.9%, 88.9% and 76.7% in unilateral cases, synchronous cases and metachronous cases, respectively. Therefore, we have recognized the importance of early discovery and treatment of contralateral breast cancer.

P53 mutations in bilateral breast carcinoma. Correlation with Ki-67 expression and the mean nuclear volume

Most investigators agree that the most common antecedent of cancer in a breast is cancer in the opposite site. Thus, the present study focused on investigating the incidence of p53 gene abnormality in bilateral breast cancer and its correlation with proliferative activity and nuclear cytomorphology to demonstrate its significance in biological behavior and predicting the relatively small percentage of second tumors in the contralateral breast. Paraffin embedded tissue specimens obtained from 18 patients with bilateral primary breast cancer were studied. Ki-67 expression, a marker of tumor cell proliferation, was scored and p53 gene abnormalities were detected by avidin–biotin–peroxidase immunostaining. The mean nuclear volume of the tumor cells was assessed by a stereologic method. p53 gene abnormalities were detected in eight cases (44.4%). Seven cases (38.8%) exhibited strong Ki-67 immunopositivity, 10 cases (55.5%) exhibited weak Ki-67 immunopositivity and one case (5.5%) exhibited negative immunostaining. The mean nuclear volume was found to be 315.9±94.3 μm 3 overall. The correlation between p53 mutations and the Ki-67 expression was statistically significant ( P=0.017, χ 2-test), whereas the assessment of the mean nuclear volume also indicated significant correlation with p53 ( P=0.024, independent-samples t-test). However, we did not find any correlation between p53 mutation and either hormone receptor status or histological grade ( P=0.52, Fisher's test and P=0.72, χ 2-test, respectively). We have concluded that p53 gene abnormalities are detected in almost half of the bilateral breast cancers and are associated with high proliferative activity and mean nuclear volume. Although so far the number of patients is too small and the follow-up too short to determine the definitive prognostic value of p53 mutation, our preliminary results have indicated that it might be an indicator of a worse prognosis in bilateral breast cancer and a predictor of cancer in the contralateral breast.

原発性両側性乳癌の臨床的特徴

原発性両側性乳癌の臨床的特徴

Mammographic appearance of cancer in the opposite breast: comparison with the first cancer.

Patients who have had cancer in one breast are at high risk for cancer in the contralateral breast. These bilateral cancers may be synchronous or metachronous. If the manifestations on mammography were similar in both breasts, an aggressive search for the mammographic findings of the first breast cancer might lead to early detection of the contralateral cancer. The purpose of this study was to evaluate mammograms for patients with bilateral cancers to determine whether the mammographic appearance of the contralateral cancer is likely to be the same as that of the first cancer. We retrospectively reviewed the pathologic and mammographic records of 69 patients with surgically proven bilateral primary breast cancer. Thirty four of 69 (49%) had synchronous cancer, and 35 (51%) had metachronous cancer. Mammographic appearances were classified as microcalcifications, spiculated mass, nonspiculated mass (whether circumscribed or poorly defined), asymmetric or developing density, architectural distortion, and normal. Multiple findings were subclassified as major and minor findings. All findings were compared between both breast cancers, and statistical significance was determined by the two-sample Z test. Forty six (67%) of 69 patients had different major mammographic findings in the contralateral cancer. Of 30 patients whose first cancers had microcalcifications, 20 (67%) had microcalcifications in the contralateral cancer. Of 39 patients whose first cancers lacked microcalcifications, 17 (44%) had microcalcifications in the contralateral cancer. This difference was statistically significant (p = .02). Of 26 patients whose first cancers had spiculated masses, 9 (35%) had a contralateral spiculated mass. Of 43 patients whose first cancers lacked spiculated masses, 12 (28%) had a contralateral spiculated mass. This difference was not statistically significant (p = .22). Our results show that contralateral tumors usually have major mammographic findings different from those of the first cancer, and the mammographic signs of the first cancer do not indicate the most likely appearance of cancer in the contralateral breast. Evaluation of a contralateral mammogram should be performed without regard for the mammographic findings for the first cancer.

THE USEFULNESS OF IMAGING DIAGNOSIS FOR SYNCHRONOUS AND PRIMARY BILATERAL BREAST CANCER -REPORT OF THREE CASES-

Three cases of synchronous and primary bilateral breast cancer in which the diagnostic imaging was very useful are described.Case 1: A 63-year-old female. A 46×36 mm tumor was palpated in the right region C, but no palpable tumor in the left breast. Ultrasonography showed a hypoechoic lesion of about 5 mm in diameter on the left breast. Intraoperative frozen section diagnosis revealed bilateral breast cancers. Case 2: A 76-year-old female. A nodule 20 mm in diameter in the right region C and a 20×20 mm tumor in the left region AE were palpated. Mammography and ultrasonography revealed an irregular shaped tumor shadow of about 9 mm on the right breast. We suspected as cancer as well as on the left breast. Case 3. A 53-year-old female. Bilateral breast nodules, a 80×80 mm nodule centering in the right region C to cover the entire breast and a 24×22 mm nodule in the left region C, were palpated. Mammography and ultrasonography revealed irregular shaped tumor shadows. Histological examination showed intraductal components in bilateral breasts of all three cases and they were diagnosed as primary bilateral breast cancer.Mammography and ultrasonography of which resolution has been improved are useful to detect breast cancer in an early stage. It is necessary to explore the contralateral breast closely with possible synchronous bilateral breast cancer in mind.

The role of mammography in the detection of bilateral primary breast cancer.

AbstractThe significance of mammography in the detection of contralateral primary breast cancer was evaluated in 55 patients with bilateral breast disease. Fifteen (65%) of 23 patients in the synchronous group and 16 (50%) of 32 patients in the metachronous group had clinically occult carcinoma in the opposite breast. Excluding the 2 malignancies discovered by prophylactic mastectomy, mammography alone was responsible for the detection of 29 (52.7%) nonpalpable, contralateral breast carcinomas. The whole series of 110 malignant breasts comprised 41 nonpalpable carcinomas, of which 12 were noninvasive [ductal carcinoma in situ (7) and lobular carcinoma in situ (5)] and the remaining 29 were invasive carcinomas, either ductal of various types (25) or lobular (4). With regard to the évaluable axillary nodes, 20 (54.1%) of 37 palpable breast cancers and only 3 (11.5%) of 26 nonpalpable breast carcinomas had positive lymph nodes. The multicentricity rate was particularly high in synchronous tumors (70.6%), and in invasive lobular (73.3%) and noninvasive (75%) carcinomas. The favorable 5‐ and 10‐year survival of patients, both in synchronous and metachronous bilateral primary breast cancer, justify that they be treated with aggressive optimism.

Family history and bilateral primary breast cancer.

The prevalence of a family history of breast cancer was established in 54 women with bilateral primary breast cancer and 208 women with unilateral disease. Women with bilateral disease had significantly greater prevalence of family history than women with unilateral breast cancer (P less than 0.01). Compared with the unilateral cancers, a significantly greater proportion of bilateral cancers had first degree affected relatives (P less than 0.05). Moreover the affected relatives of probands with bilateral disease showed a significantly higher prevalence of bilateral breast cancer compared with the relatives of women with unilateral disease (P = 0.04). The findings suggested that bilateral disease was a characteristic of familial breast cancer.

Survival in bilateral breast cancer.

The presence of bilateral invasive breast cancer places the patient in a state of double jeopardy. At Memorial Sloan-Kettering Cancer Center, the overall 10-year recurrence rate for unilateral Stage I breast cancer was 16%, whereas the recurrence rate for simultaneous, bilateral Stage I breast carcinoma was 29%: almost twice as high. The average 10-year survival of all patients with negative axillary nodes was 57%. In this retrospective analysis of 403 patients with bilateral primary operable breast cancer treated at Memorial Sloan-Kettering Cancer Center, significant differences were noted in the disease-free survival between patients with bilateral noninvasive cancer, bilateral invasive cancer, and the combination of invasive and in situ cancers. Bilateral intraductal cancer and lobular carcinoma in situ offered an excellent prognosis. The combination of preinvasive cancer on one side and infiltrating carcinoma on the other had the next best survival. The in situ lesion, when treated by mastectomy, did not alter the patients' life expectancy from that of the general population with unilateral breast cancer, thus indicating that surgeons should strive to detect breast cancer in its preinvasive form. The 5- and 10-year relapse-free survival of patients with bilateral invasive disease, regardless of axillary nodal status and tumor size, was 60% and 51%, respectively, for patients with a bilateral presentation and 54% and 38%, respectively, for carcinomas presenting metachronously. More important in determining prognosis, however, was the number of axillary nodes involved and the level of involvement. Invasion of bilateral axillary nodes at all levels predicted a poor prognosis. Because of this shortened survival, systemic adjuvant therapy should be considered for patients with bilateral invasive disease. The most common preinvasive breast cancer was lobular carcinoma in situ and the most frequently invasive tumor was infiltrating duct cancer. Since a contralateral breast cancer at the time of definitive treatment of the first side does not always present as a mass or with positive mammography, a random biopsy of the second breast is recommended. This should be done in the upper, outer quadrant and should include the subareolar area. With prompt adequate treatment, it is expected that survival from bilateral breast cancer should improve.

Breast parenchymal patterns in women with bilateral primary breast cancer

Breast parenchymal patterns in women with bilateral primary breast cancerM. A. Chaudary, I. H. Gravelle, J. C. Bulstrode, D. Y. Wang, R. D. Bulbrook, R. R. Millis and J. L. HaywardM. A. ChaudaryImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this author, I. H. GravelleImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this author, J. C. BulstrodeImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this author, D. Y. WangImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this author, R. D. BulbrookImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this author, R. R. MillisImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this author and J. L. HaywardImperial Cancer Research Fund, Breast Cancer Unit, Guy's Hospital, London, SE1 9RTSearch for more papers by this authorPublished Online:28 Jan 2014https://doi.org/10.1259/0007-1285-57-674-195-aSectionsPDF/EPUB ToolsAdd to favoritesDownload CitationsTrack Citations ShareShare onFacebookTwitterLinked InEmail AboutAbstractIn our recent paper (Chaudary et al, 1983) we failed to mention the source of the mammograms which were taken of the breast cancer patients. Previous article Next article FiguresReferencesRelatedDetails Volume 57, Issue 674February 1984Pages: 111-B8 © The British Institute of Radiology History ReceivedNovember 01,1983Published onlineJanuary 28,2014 Metrics Download PDF

Breast parenchymal patterns in women with bilateral primary breast cancer.

Mammograms were obtained from 44 women aged over 30 years with bilateral primary breast cancer, 60 women with unilateral breast cancer, matched for age and menopausal status with the bilateral cases, and 937 normal women, again all aged over 30 years. The mammograms were classified according to Wolfe's criteria. Both groups of cancer patients were found to have a significantly (p less than 0.05) greater proportion of pre-menopausal women with the DY type of breast parenchymal pattern compared with the normal pre-menopausal women. No association was found between the P2 mammographic pattern and breast cancer. The study failed to show any difference in the distribution of mammographic risk categories in women with bilateral disease and those with unilateral cancers only.

BILATERAL BREAST CANCER

Fifteen patients with bilateral breast cancer were clinically analyzed on the basis of a result of surgical treatment, in whom eight patients had bilateral synchronous breast cancer, four were non-synchronous and the remaining three were metastatic breast cancer, respectively. The prognosis of patients with bilateral breast cancer was not pessimistic, indicating that it depended on the disease stages of each cancer. On the other hand, it was emphasized that the prognosis of patients with bilateral metastatic breast cancer was extremely poor. Surgeons should be aware of high risk of contralateral breast cancer in careful follow-up following mastectomy for breast cancer. It is generally accepted that patients with cancer of one breast have a higher than average risk of developing cancer of the opposite breast. It is not so rare that bilateral breast tumors are seen in an identical patient on account of the effectiveness of high resolution mammography and sonography in early detection. It is known that a cancer of one breast means the most frequent precancerous lesion of the opposite breast. Bilateral breast cancer may occur in any of the following ways. 1. Bilateral simultaneous breast cancer occurring independently in both breasts and at the same time (syncronous). 2. Bilateral primary non-simultaneous breast cancer occurring independently in each breast but at different times (asynchronous). 3. Bilateral secondary breast cancer occurring either simultaneously or non-simultaneously but as one of the manifestations of metastatic dissemination. However, despite these simple definitions, there is often great difficulty in determining the exact type of bilateral breast cancer under consideration, in particular, identifying second primary cancer from metastatic one. In this study, bilateral breast cancers were clinicopathologically reviewed on the basis of a result of surgical treatment at the First Department of Surgery, Nagasaki University School of Medicine.

Bilateral breast cancer and familial aggregations

Bilateral breast cancer and familial aggregation among Japanese female patients with breast cancer were studied and results were compared with those among American female patients. Out of 3365 female patients with breast cancer mastectomized at the Cancer Institute Hospital, Tokyo from 1946 to 1975, 92 cases were primary bilateral breast cancer. The crude incidence of bilateral cancer was 2.7%, whereas it was reported to range between 3.0% and 6.8% among American female patients. The true incidence rate of breast cancer after operation for unilateral breast cancer was calculated to be 3.4 per 1000 Japanese patients per year, while it was reported to be between 5.8 and 7.1 among American patients. These figures for American patients are roughly twice as large as those for Japanese females. In the bilateral breast cancer group, there was a high frequency of familial history of breast cancer, about three times higher than that in the unilateral breast cancer group. Further, in the bilateral breast cancer group, about half of the patients were nulliparous and 60% of the patients had breast cancers associated with fibrocystic disease in the same breast tissues. These figures were about three times greater than for those in the unilateral breast cancer group.

Bilateral primary breast cancer

Bilateral primary breast cancer

Bilateral Primary Breast Cancer

Primary carcinoma of breast was treated in 967 patients from 1962 through 1972. Thirty-five of these patients had a second primary tumor of which 50% were discovered simultaneously. A family history for cancer was recorded in 26% of the patients with bilateral cancer. Patients found their tumor more often than the physician except in the simultaneous cases where the physician was more successful. Pathological examination showed 10% of the tumors were comedo, lobular carcinoma in situ, papillary, or tubular cancers. In the metachronous group, 50% of the axillae were involved on both sides. In the simultaneous cases the axilla was less frequently involved. Mammography, biopsies of the second breast, and prophylactic mastectomy in certain high-risk patients should improve survival rates.

Bilateral breast cancer at the Johns Hopkins Hospital. A discussion of the dilemma of contralateral breast cancer.

A study of 490 cases of breast cancer at the Johns Hopkins Hospital revealed 42 cases (8.6%) with bilateral disease. There were 8 cases (1.7%) of bilateral primary simultaneous breast cancer and 34 cases (6.9%) of bilateral primary non-simulaneous breast cancer. There were 6 cases of lobular carcinoma in situ included in this series; 3 cases were simultaneous and 3 cases were non-simultaneous. If these 6 cases were deleted from the study, the total incidence of bilateral breast cancer would be 7.3%. A similar study of 67 cases of breast cancer in private patients revealed only 1 case (1.5%) with bilateral breast cancer over a long period of follow-up. The incidence of latent or occult cancer of the contralateral breast is discussed in relation to the incidence of overt bilateral breast cancer. Careful follow-up examination is the recommended method of management for all patients with primary breast cancer. Periodic physical examinations supplemented by mammography and other meaningful diagnostic aids (thermography, xeroraadiography, and ultrasonography) are to be preferred to random biopsy or prophylactic mastectomy of the asymptomatic contralateral breast.

BILATERAL PRIMARY BREAST CANCER; A PROSPECTIVE CLINICOPATHOLOGICAL STUDY.

A prospecitve 20-year study on the occurrence of bilateral breast ca ncer is presented. Among 1458 patients treated at Memorial Hospital New York 1940-1943 follow-up has proved a primary cancer in both breasts in 91. Incidence has averaged 7 patients per year per 1000 patients at risk. It is thought that overall frequency may have been greater than recorded. Women less than 50 years of age at the time of first mastectomy had about twice the risk as women who were over 60. The overall risk of a second cancer is 5 times greater than that of breast cancer in the general female population. It is 10 times normal for women less than age 50 but under 2 times normal after age 70. Women who have survived their first cancer (5-year survival) and are presently alive have an average life expectancy of another 15 years. The story for many is only half told but the risk tends to decrease with age. There has been development of a second breast cancer for each 8 deaths from the first cancer or 1 for each 3 deaths from other causes. About 1 in every 10 in the original series will be affected despite deaths fro m recurrence of the first cancer and other causes. The highest incidenc e was found among patients who had multiple cancers in the first breast. When the first tumors were low-grade duct cancers incidence of second cancers was least. When first tumors were comedocarcinomas or colloid carcinomas incidence was highest. Mixed patterns including mixed grades were common. Patients with metastases at bilateral cancers to develop. Second cancers had fewer metastases. They tended to resemble first cancers in type. The observed 20-year survival rate was 27%. Despite all the follow-up efforts 66% of the second cancers were not early when removed. Second cancers acting in conjuction with recurrence of the first cancer almost halved the survival expected. The greater the gains in early diagnosis and salvage from first cancers the more important become the second ones. The early years after the first mastectomy are the primary time for second cancers to appear.