Comparison of Clinicopathological Characteristics Between Primary and Contralateral Cancers in BRCA1/2 Carriers with Metachronous Bilateral Breast Cancers / 肿瘤防治研究

Objective To compare the clinicopathological characteristics between primary and contralateral cancers in patients with metachronous bilateral breast cancer (MBBC) who carried a BRCA1/2 germline pathogenic variant. Methods A total of 496 BRCA1/2 carriers with primary unilateral breast cancer were included (196 with BRCA1 and 300 with BRCA2). Clinicopathological information of patients was collected, and the median follow-up for the entire cohort was 10.4 years (0.4-20.8 years). Results Among all patients, 31 (15.8%) of the 196 BRCA1 carriers and 49 (16.3%) of the 300 BRCA2 carriers had MBBC, respectively. Among the 31 BRCA1 carriers who developed MBBC, the proportion of triple-negative breast cancer (TNBC) in primary cancer and contralateral cancer was 61.3% and 67.7%, respectively. If the primary cancer of BRCA1-mutated MBBC was TNBC, the probability of the contralateral breast cancer with TNBC was 89.5% (17/19), which was significantly higher than that if the primary cancer was non-TNBC (33.3%, 4/12) (P=0.004). Among the 49 BRCA2 carriers who developed MBBC, the predominant molecular phenotype of the primary and contralateral cancers was HR+ & HER2- (77.6% and 67.3%, respectively; P=0.53). Conclusion Approximately 60% of BRCA1 carriers exhibit TNBC. If a BRCA1 carrier with a TNBC primary breast cancer had an MBBC, the probability of the contralateral breast cancer being TNBC phenotype is almost 89.5%.

Dosimetric comparison between dIMRT and VMAT for bilateral breast cancer / 中国辐射卫生

Objective To compare the dosimetric difference of target and organs-at-risk between intensity-modulated radiotherapy (dIMRT) and volumetric modulated arc therapy (VMAT) for bilateral breast cancer, so as to discuss the clinical feasibility of radiotherapy for bilateral breast cancer. Methods The clinical data of 18 patients receiving radical or modified radical mastectomy for confirmed bilateral breast cancer were enrolled in this study. dIMRT plans and VMAT plans were designed for each patient, and discuss the dosimetric data of two radiotherapy plans. Results Both the two plans satisfied the prescription. In terms of the homogeneity index, VMAT plans (0.09 ± 0.02) were superior to dIMRT plans (0.11 ± 0.01, P < 0.05). In terms of the conformity index,VMAT plans (0.82 ± 0.52) were superior to dIMRT plans (0.71 ± 0.51, P < 0.05). Furthermore, VMAT plans (0.98 ± 0.06) were superior to dIMRT plans (1.24 ± 0.08, P < 0.05) in the dose gradient index. The V10、V20、V30 and Dmean of lungs in VMAT plans (39.07 ± 4.92，22.19 ± 4.36，12.81 ± 4.71，1309.03 ± 135.55) were higher than those in dIMRT plans (30.34 ± 4.26，17.56 ± 4.31，6.77 ± 3.93，1201.39 ± 166.77, P < 0.05).Meanwhile, the V5 of lungs in VMAT plans (63.36 ± 9.02) was higher than that in dIMRT plans (58.01 ± 7.17, P > 0.05). However, the V5、V30 and Dmean of heart in VMAT plans (51.98 ± 3.60，3.78 ± 1.76，885.89 ± 59.84) were lower than those in dIMRT plans (77.16 ± 12.11，5.22 ± 2.85，1036.96 ± 151.46, P < 0.05). The Dmax of spinal cord in VMAT plans (2150.42 ± 136.19) was significantly lower than that in dIMRT plans (3008.23 ± 304.15, P < 0.05). Monitor units in VMAT plans（792.61 ± 62.53）was significantly lower than that in dIMRT plans (3225.33 ± 498.66, P < 0.05). Conclusion Although VMAT has many advantages: achieves better homogeneity index and conformity index of target areas, reduces the irradiation dose of organs-at-risk, especially, the irradiation dose of heart and spinal cord is significantly reduced, however, it increases the irradiation dose of lungs. To reduce the recurrence of grade ≥ 2 radiation pneumonia, dIMRT should be better considered in the application of radiotherapy for bilateral breast cancer.

Rapid ARC Radiotherapy in a Patient with Bilateral Breast Carcinoma - 10 Year Follow UP

Introduction: A patient with synchronous bilateral breastcancer was treated with Rapid arc (Volumetric Modulated Arctherapy - VMAT) radiotherapy following breast conservationsurgery. She is alive and without radiotherapy complicationsin the 10 year follow up period.Case report: A 51 year old lady presented with synchronousbilateral breast cancer. She underwent wide excision of bothbreast lumps with bilateral axillary lymph node sampling(Invasive Ductal Carcinoma, pT1N1 in left breast and pT2N0in right breast). She was treated with adjuvant chemotherapyand post-operative radiotherapy to both breasts with rapidarc (VMAT) technique in August 2009. The radiotherapyplanning was compared among Three Dimensional ConformalRadiotherapy, Intensity Modulated Radiotherapy and Rapidarc techniques. Details of dose homogeneity and sparing ofOrgans at risk are discussed. She tolerated the treatment wellwithout major toxicity. She has been on regular follow up tillher last visit in June 2019. She was also treated for surgeryfollowed by radiotherapy for Carcinoma of cervix 12 yearsago.Conclusion: This case is presented for the novel radiotherapytechnique in treating bilateral breast cancer resulting in goodquality of life and long term survival.

Cáncer de mama bilateral, ¿una sola enfermedad? Concordancia de receptores hormonales / Bilateral breast cancer, a single disease? Concordance of hormonal receptors

Introducción El incremento del diagnóstico de cáncer de mama en estadios tempranos conduce a un mejor pronóstico y, por ende, a una mayor expectativa de vida, situación que posibilitaría el desarrollo de un segundo tumor contralateral. Las mujeres con cáncer de mama tienen tres a cuatro veces mayor riesgo de desarrollar un cáncer en la mama contralateral. La patogénesis de la bilateralidad no está del todo clara; las correlaciones en el subtipo histológico, el grado tumoral y el estado de los Receptores Hormonales entre los dos tumores se han considerado indicativos de que se originan de una sola célula (teoría de origen monoclonal) con diseminación metastásica secundaria hacia la mama opuesta. Por otro lado, su discordancia llevaría a considerarla una lesión independiente del tumor primario (teoría de origen multiclonal). Dependiendo del tiempo de aparición entre un tumor y el otro, suelen ser de tipo sincrónico (cmbs) y metacrónico (cmbm). Objetivo Nuestro objetivo es describir las características clínico-patológicas y la concordancia de los Receptores Hormonales entre ambos tumores. Material y método Se llevó a cabo un estudio de corte transversal y retrospectivo en dos centros, el Hospital General de Agudos Dr. Ignacio Pirovano (hgaip) y Consultorio de práctica privada (pp) en el periodo comprendido entre el 1º de agosto de 2006 y el 1º de diciembre de 2014. Los datos fueron recabados de la base de datos del Registro de Cáncer de Mama (rcm) de la Sociedad Argentina de Mastología de ambas sedes. Resultados Identificamos 1.282 pacientes con cáncer de mama tratadas en hgadip (958) y pp (324) en dicho período. Encontramos 50 casos de cáncer de mama bilateral (3,9%), de los cuales 38 (2,96%) fueron de tipo metacrónico y 12 (0,94%) de tipo sincrónico. La edad media de presentación fue similar en ambos grupos (p=0,43): 52 años para el cmbm y 54 años para el cmbs. El 29% y el 41,6 % de las pacientes tenían antecedentes familiares de cáncer de mama en los cmbm y cmbs respectivamente (p=0,43). El primer tumor metacrónico fue palpable en el 71% de las pacientes y el segundo tumor metacrónico en el 7,9% (p<0,05). En cuanto a los sincrónicos, en todos los casos se presentaron como tumor palpable en una de las mamas y en un 58% como tumor no palpable en la mama contralateral. En el primer tumor metacrónico fue más utilizada la cuadrantectomía (44,7%) y el vaciamiento axilar (55,3 %); en cambio, en el segundo tumor metacrónico, se realizó la biopsia radioquirúrgica (60,5%) y el ganglio centinela (84,2%) (p<0,05). Para los sincrónicos, la cirugía más utilizada en el tumor dominante fue la mastectomía (41,7%) y la biopsia radioquirúrgica (33%) en el tumor contralateral; el ganglio centinela fue realizado en el 41,7% de las pacientes tanto en el tumor sincrónico dominante como en el contralateral. El tipo histológico predominante fue el carcinoma ductal invasor tipo nos: 57,9% en el primer tumor metacrónico, 65,8% en el segundo tumor metacrónico, 91,6% en el tumor sincrónico dominante y 41,6% en el tumor sincrónico contralateral. Se observó carcinoma ductal in situ (cdis) asociado: en el 36,8 % en el primer tumor metacrónico, en el 44,7% en el segundo tumor metacrónico, en el 25% en el tumor sincrónico dominante y en el 50% del sincrónico contralateral. El grado histológico (gh) predominante fue gh1 en el cmbm y gh3 en el cmbs. Los tratamientos adyuvantes más utilizados en el primer tumor metacrónico fueron la radioterapia en el 79%, la quimioterapia en el 68,4% y el tamoxifeno en el 60,5%; en el segundo tumor metacrónico el uso de la radioterapia fue casi similar (81,5%), disminuyó la utilización de quimioterapia adyuvante y de tamoxifeno, ambos a un 42,1%, y el uso de Inhibidores de Aromatasa se incrementó al 52,6%. El 58,3% de las pacientes con cmbs requirió radioterapia y el 75% quimioterapia adyuvante y tamoxifeno. El 86,8% de los primeros tumores metacrónicos fue positivo para re y rp, el 10,6% fue negativo para ambos y el 2,6% fue re positivo y rp negativo. En el segundo tumor metacrónico, el 92,1% fue positivo para re y rp, el 5,2% fue negativo para ambos y solo el 2,6% se presentó como re positivo y rp negativo. En el análisis de concordancia, se observaron 32 pares metacrónicos concordantes positivos para re, 2 pares metacrónicos discordantes positivo/negativo y 4 pares metacrónicos discordantes negativo/positivo. La relación fue similar para los re: 30 pares metacrónicos concordantes positivos, 3 pares metacrónicos discordantes positivo/negativo y 5 pares metacrónicos discordantes negativo/positivo. Se observó que el 58,4% de los tumores sincrónicos dominantes expresó re y rp positivos, y el resto (41,6%) fue negativo para ambos; en el tumor sincrónico contralateral, fue casi similar: el 66,7% de los casos expresó re y rp positivos y el 33,3% fue negativo para ambos. Se observaron 7 pares sincrónicos concordantes positivos para re y rp, 4 pares sincrónicos concordantes negativos para ambos y solo un par sincrónico discordante negativo/positivo. Conclusiones La gran mayoría de las pacientes fue diagnosticada con cáncer de mama bilateral como lesión subclínica en la mama contralateral por mamografía tanto en los metacrónicos como en los sincrónicos. No se ha demostrado que el riesgo disminuya a lo largo del tiempo, por lo que se destaca la importancia del seguimiento a largo plazo como pilar fundamental para la detección temprana del cbmm que probablemente tenga un impacto favorable en la supervivencia. La concordancia en la expresión de re y rp para el cmbm fue alta (79%) y para el cmbs fue aún mayor (92%), lo que podría reflejar un efecto del microambiente hormonal que influya tanto para la iniciación como para el desarrollo de estas lesiones de forma simultánea e independiente del origen único o multiclonal

Introduction The increase of the diagnosis in the early stages of breast cancer leads to a better prognosis and therefore a longer life expectancy, a situation that would allow the development of a second contralateral tumor. Women with breast cancer have three to four times greater risk of developing cancer in the contralateral breast. The pathogenesis of bilateral breast cancer is not entirely clear; correlations in the histologic subtype, tumor grade and Hormonal Receptor status between the two tumors have been considered as an indicative of single cell origin (Monoclonal origin theory) with secondary metastatic spread to the opposite breast; the discordance of those parameters would consider an independent lesion of the primary tumor (theory of multiclonal origin). They are named synchronous and metachronous depending on the time of onset. Objective Our study aims to describe the clinical-pathological characteristics and the concordance of the Hormonal Receptor status. Materials and method A cross-sectional and retrospective study was carried out at two centers, "Hospital General de Agudos Dr. Ignacio Pirovano" (hgaip) and private practice (pp) in the period from August 1, 2006 to January 1, December 2014. The data were collected from the database of "Registro de Cancer de Mama" (rcm) of the Argentine Society of Mastology (sam) from both centers. Results We identified 1,282 breast cancer patients treated in hgadip (958) and pp (324). We found 50 cases with bilateral breast cancer (cmb) (3.9%); 38 patients (2.96%) were metachronous and 12 patients (0.94%) synchronous. The mean age of presentation was similar in both groups (p = 0.43): 52 years old for cmbm and 54 in the cmbs group. The 29% and 41.6% of the patients had a breast cancer family history in the cmbm and cmbs respectively (p=0.43). The first metachronous tumor was clinically palpable in 71% of the patients and in the second one in 7.9% (p <0.05). In synchronous tumors, all cases were clinically palpable in one side of the breast and in 58% were subclinical in the contralateral side. In the first metachronous tumor, the quadrantectomy (44.7%) and the lymphadenectomy (55.3%) were more commonly used; on the other hand, in the second metachronuos tumor, the radio-surgical biopsy (60.5%) and sentinel lymph node (84.2%) were more executed (p <0.05). For the synchronous, the dominant tumor had more frequently a mastectomy (41.7%) and in the contralateral tumor the radio-surgical biopsy was executed in 33%; sentinel lymph node was performed in 41.7% in both synchronous tumors. The predominant histological type was the invasive ductal carcinoma nos type: 57.9% of the first metachronous tumor, 65.8% of the second metachronous tumor, 91.6% of the dominant synchronous tumor and 41.6% of the contralateral synchronic tumor. Ductal carcinoma in situ (dcis) was associated in 36.8% in the first metachronous tumor, 44.7% in the second metachronous tumor, 25% in the dominant synchronous tumor and 50% in the contralateral synchronic tumor. The predominant histological grade (gh) was gh1 in cmbm and gh3 in cmbs. The adjuvant treatments used for the first tumor were radiotherapy in 79%, chemotherapy in 68.4% and Tamoxifen in 60.5%. For the second metachronous tumor, the use of radiotherapy was almost similar with 81.58%, and the use of adjuvant chemotherapy and Tamoxifen decreased both at 42.11%; the use of Inhibitors of Aromatase increased to 52.6%.The 86.8% of the first metachronous tumors were er and pr positive, the 10.5% were both negative, the 2.6% were er positive and pr negative. In the second metachronous tumor, the 92.1% were er and pr positive, 5.2% were both negative and 2.6% were er positive and pr negative. In the concordance analysis, we observed 32 concordant metachronous pairs of er positive, 2 discordant metachronous pairs of positive / negative and 4 discordant metachronous pairs of negative / positive. We had similar results for pr, with 30 concordant metachronous positive pairs, 3 discordant metachronous pairs of positive / negative and 5 discordant metachronous pairs of negative / positive. The 58.4% of the dominant synchronous tumors expressed er and pr positive and in the rest (41.6%) were both negative. In the contralateral synchronous tumor it was observed that 66.7% of the cases expressed er and pr positive and 33.3% were negative for both. We found 7 concordant synchronous pairs of er and pr positive, 4 concordant synchronous pairs negative for both and only 1discordant synchronous pair negative / positive Conclusions In a big amount of the patients, the contralateral breast cancer was diagnosed as a subclinical lesion by mammography in the metachronous and synchronous tumors. It has not been demonstrated that the risk decreases over the time, which highlights the importance of long-term follow-up for early detection of cmbm that probably has more favorable impact on survival. The concordance of er and pr expression for cmbm was high (79%) and for cmbs was even higher (92%), that may reflect a particular hormonal environment effect that influences both initiation and development of these lesions simultaneously and independently of single or multiclonal origin

Primary synchronous bilateral breast cancer.

Background: Primary synchronous bilateral breast cancer (PSBBC) is a rare clinical entity. The reported incidence ranges between 0.3% and 12%. There are several controversial issues regarding PSBBC pertaining to the diagnostic criteria, nomenclature, and management policies. Materials and Methods: Fourteen cases of PSBBC treated between 2001 to 2010 at our institute were retrospectively analysed in regards to demographic data, management and follow up. Results: PSBBC constituted 0.19% of total breast cancer patients at our institute. Age ranged from 28 to 78 years. PSBBC were detected by clinical examination in eight cases and by mammography in six cases. Twelve patients underwent bilateral modified radical mastectomy, one had unilateral mastectomy on one side and breast conservation on the other side and one patient has bilateral breast conservation. Majority of patients belonged to stage 2 and stage 3. All patients were found to have invasive ductal carcinoma. Five cases were ER/PR positive and 8 patients were triple hormone receptor negative. Eight patients received unilateral and six received bilateral adjuvant radiotherapy. Nine patients received adjuvant chemotherapy. 5 patients received adjuvant hormonal therapy. Median follow up of patients was 15.4 months. Conclusion: PSBBC is a rare event warranting awareness and screening of the contralateral breast in patients with unilateral breast cancer. These patients require individualized treatment planning based on the tumor factors of the index lesion. Further multi institutional prospective studies are needed for adequate understanding of management of PSBBC.

Research progress on bilateral breast cancer / 国际肿瘤学杂志

Women diagnosed with breast cancer have a significantly higher risk of developing contralateral breast carcinoma.When the dignosis ofbilateral breast cancer (BBC)is established,the challenges for the doctors are to determine contralateral breast carcinoma is metastasis or primary lesions.The pathological type,receptor status,biological behavior and the prognosis of bilateral breast cancer are the issues have to be considered.On the other hand,we discuss which type of breast cancer trend to be bilateral breast cancer,thus more effective follow-up and preventive procedures would be applied on this part of patients to improve their quality of life and the curative rate.

Cáncer de mama bilateral en el Hospital Universitario Comandante Manuel Fajardo, 1982-2003 / Bilateral breast cancer at Comandante Manuel Fajardo Teaching Hospital (1982-2003)

En 1945, Foote y Stewart plantearon que el antecedente más frecuente de cáncer en un seno es haber tenido una neoplasia en el seno contrario. Se realizó un estudio sobre los casos de cáncer de mama bilateral atendidos en nuestro servicio entre 1982 y 2003. Métodos: El universo de nuestro trabajo está compuesto por 25 pacientes que fueron atendidas en los últimos 20 años por cáncer de mama bilateral, la mayoría de ellos metacrónicos (21 casos). En cada caso se analizó edad, etapas clínicas al momento del diagnóstico, tratamiento utilizado, tipo histológico y evolución, entre otras variables. Resultados: Se observó la mayor incidencia de esta enfermedad en la 5ta. y 6ta. décadas de la vida, con predominio de los tumores en etapa II. El tipo de operación más realizado fue la mastectomía radical modificada de Patey y prevalecieron las técnicas más conservadores en la segunda operación. Siete de las pacientes fallecieron por la enfermedad. Conclusiones: El pronóstico de las mujeres con cáncer de mama bilateral suele ser favorable y depende de la etapa de desarrollo de éste al momento del diagnóstico. El tratamiento del segundo primario fue más conservador que el primero. El seguimiento estricto y el uso de la ingeniería genética son elementos fundamentales para el diagnóstico precoz(AU)

In 1945, Foote and Stewart said: the most frequent antecedent of cancer in a breast is having had a neoplasia in the other breast. A study of the cases of bilateral breast cancer seen in our service between 1982 and 2003 was conducted. Methods: The universe of our work was composed of 25 patients attended in the last 20 years due to bilateral breast cancer. Most of them were metachronic (21 cases). Age, clinical stages at the time of diagnosis, treatment used, histological type and evolution, among other variables, were analyzed. Results: the highest incidence of this disease was observed in the 5th and 6th decades of life, with predominance of stage II tumors. Patev's modified radical mastectomy was the most common operation. The most conservative techniques prevailed in the second operation. Seven of the patients died as a result of the disease. Conclusions: the prognosis of women with bilateral breast cancer is usually favorable and it depends on its development stage at the time of the diagnosis. The treatment of the second was more conservative than the first one. The strict follow-up and the use of genetic engineering are fundamental elements for the early diagnosis(AU)

Clinical and pathological analyses of estrogan receptor and progestin recetor expressions in bilateral breast cancer / 第三军医大学学报

Objective To investigate the relationship between clinical and pathological features in order to observe estrogen and progestin receptor(ER and PR) expressions in bilateral primary breast cancer(BPBC). Methods ER and PR expressions in 29 cases of BPBC from 1990 to 2003 and the clinical and pathological features were analyzed retrospectively. Results ER and PR positive expressions were 53 2% and 41 2% in unilateral breast cancer, but 69% and 51% in first primary cancer of BPBC, and 65% and 41 3% in second primary cancer of BPBC, respectively. Invasive lobular carcinoma(ILC) was 11 6% in unilateral breast cancer and 34 4% in first cancer of BPBC and 41.3% in second primary cancer of BPBC. Status of lymph nodes in unilateral breast cancer was similar to that in BPBC. Conclusion There is higher ER expression in BPBC than that in unilateral breast cancer. ILC is significantly related to the carcinogenesis of BPBC. The status of lymph nodes is not related to BPBC.

Bilateral Breast Carcinoma after Treatment with Immunosuppressant

Bilateral breast cancer developed in a 45-year-old woman who received a renal transplant followed by immunosuppression with Cyclosporine. She underwent a left modified radical mastectomy, and right breast conserving surgery, with both axillary lymph nodes being dissect. Few cases have been reported on breast cancer associated with renal transplantation. Although a causal relationship with immunosuppression therapy and breast carcinoma was not implied, a heightened awareness of the possible coexistence of immunosuppression therapy and breast carcinomas are necessary.

Prognostic factors in bilateral breast cancer / 中国癌症杂志

Purpose:To study the determining prognostic factors that affect the survival of patients with bilateral breast cancer. Methods:The records of 21 women with bilateral breast cancer were analyzed.4(19%) presented simultaneous bilateral tumor.17(81%)developed bilateral breast cancer with interval in between. Patients were treated with surgery, radiation treatment and chemotherapy. Analysis of high risk factors of breast cancer and possible relation to postoperative survival was carried out.Results:The size of the tumor, the number of involved axillary nodes, and the adequacy of the initial treatment still remain the major prognostic factors ,correlated with the time interval between two cancers. 2 year, 5 year, 10 year, survival was recorded to be 90%, 71.4%, 66.7%. Conclusions:If treatment is correct for bilateral breast cancers, its 5 year survival rate still rather high. Time interval between two breast cancers was the most prominent prognostic factor, correlated with the overall survival. The early diagnosis and prompt adequate treatment of the seconed primary breast cancer are still the key to longer survival rates of bilateral breast cancer.

Bilateral Breast Cancer

Among the 1760 cases of carcinomas of the breast treated between 1981 and 1996, there were 31 cases of bilateral breast cancer. Of these, 7 were synchronous tumors and the remaining 24 patients had metachronous tumors : 41.7% of all patients had presented within 5 years since the first primary tumors were detected and 73.3% of all patients had presented within 10 years. The mean age of the synchronous bilateral cancers was 39.9 (26~55), and the mean age at the diagnosis of the first cancers in the metachronous cancers was 44.75 (31~70) years old. The location of the tumor was the same in 64% and 68% of the synchronous and metachronous cancers, respectively, that had an identified histology. The mean survival of metachronous group was 70.5 months and that of synchronous group was 114.7 months. However, there was no statistical significance between the mean survival times of the two groups (p>0.05). We recommend a careful check-up for the opposite breast at the time of primary cancer treatment, as well as well an organized follow-up program for all patients having undergone treatment for breast cancer. Further investigations are required to determine the incidence of and risk factors for second cancer development in the opposite breast.