|Year : 2016 | Volume
| Issue : 1 | Page : 67-71
A rare case of triple negative synchronous bilateral invasive ductal carcinoma of breast
Abhishek Purkayastha, Neelam Sharma, Nishant Lohia
Department of Radiation Oncology, Army Hospital Research and Referral, New Delhi, India
|Date of Web Publication||2-Jun-2016|
Department of Radiation Oncology, Army Hospital Research and Referral, Dhaula Kuan, Delhi Cantonment - 110 010, New Delhi
Source of Support: None, Conflict of Interest: None
The occurrence of bilateral breast carcinoma is extremely rare with an incidence of 2-5% of all breast malignancies. We hereby report an unusual and interesting case of triple negative synchronous invasive ductal carcinoma (IDC) of bilateral breasts detected simultaneously in view of its rarity and therapeutic challenge it presented. A 55-year-old postmenopausal female presented with a history of lump bilateral breasts of 4 months duration. Fine needle aspiration cytology of both breast lumps showed IDC. Mammography showed Breast Imaging Reporting and Data System V both breasts. Metastatic workup was negative. She underwent bilateral modified radical mastectomy. Postoperative histopathology revealed IDC Grade III with estrogen receptor, progesterone receptor and human epidermal growth factor receptor 2-neu negative on immunohistochemistry. She received adjuvant chemotherapy followed by locoregional radiotherapy to the right breast in view of nodal positivity. Presently on regular follow-up without any evidence of local recurrence or distant metastasis.
Keywords: Bilateral breast carcinoma, invasive ductal carcinoma, metachronous, radiotherapy, synchronous
|How to cite this article:|
Purkayastha A, Sharma N, Lohia N. A rare case of triple negative synchronous bilateral invasive ductal carcinoma of breast. Arch Med Health Sci 2016;4:67-71
|How to cite this URL:|
Purkayastha A, Sharma N, Lohia N. A rare case of triple negative synchronous bilateral invasive ductal carcinoma of breast. Arch Med Health Sci [serial online] 2016 [cited 2021 Feb 26];4:67-71. Available from: https://www.amhsjournal.org/text.asp?2016/4/1/67/183345
| Introduction|| |
Bilateral breast carcinomas are rare  and can be synchronous or metachronous while simultaneously appearing lesions are least heard of. Invasive ductal carcinomas (IDCs) are rarer than lobular carcinomas which have more propensities to turn bilateral. Although prophylactic surgery, chemotherapy, or hormonal therapy may reduce this risk of bilaterality, there are no established studies regarding the role of radiotherapy (RT) or lifestyle modifications, reproductive, dietary or other factors as prophylactic or definitive measure. In view of increased lifespan of women with first breast primary, analytical studies addressing the possible risk factors involved in the development of contralateral breast carcinoma is necessary.
| Case Report|| |
A 55-year-old postmenopausal female with no known comorbidities, P2 L2, all full term normal delivery, both girls with last child 16-year-old presented with complaints of incidentally detected lump bilateral breasts of 4 months duration. She had no family history of any breast lump or breast carcinoma. Clinical evaluation revealed 4 cm × 3 cm firm lump left breast upper inner quadrant and a 5 cm × 4 cm firm lump right breast upper outer quadrant with no skin involvement. No axillary lymph nodes (LNs) were palpable on both sides.
Fine needle aspiration cytology of both breasts showed infiltrative ductal carcinoma. Mammography bilateral breasts showed Breast Imaging Reporting and Data System Grade V both breasts [Figure 1]. Ultrasonography (USG) bilateral breasts [Figure 2] showed irregular marginated hypoechoic lesions 3.2 cm × 3.9 cm × 3.9 cm left breast and 4.2 cm × 4.0 cm × 3.8 cm right breast causing architectural distortion. USG abdomen and pelvis showed normal findings. Metastatic workup with whole body positron emission tomography (PET) scan showed localized disease.
|Figure 1: Mammography bilateral breasts showing Breast Imaging Reporting and Data System (BIRADS) V|
Click here to view
|Figure 2: Ultrasonography of bilateral breasts showing irregular marginated hypoechoic lesions causing architectural distortion|
Click here to view
She was diagnosed as carcinoma bilateral breast cT2N0M0 stage IIA left breast and cT3N0M0 IIB right breast and underwent upfront bilateral modified radical mastectomy (MRM). Postoperative histopathology report (HPR) of right breast [Figure 3] showed IDC Grade III, Modified Bloom-Richardson (MBR) Score of 3 + 3 + 3 = 9/9, one out of nine axillary LN positive for tumor deposits pT2N1M0 while HPR of left breast [Figure 3] showed IDC Grade III, MBR Score 3 + 3 + 3 = 9/9, all 10 dissected axillary LNs negative for tumor, margins negative pT2N0M0. Immunohistochemistry revealed estrogen receptor (ER), progesterone receptor (PR) and human epidermal receptor protein-2 (HER 2) staining negative with Ki-67 30-40%.
|Figure 3: Postoperative histopathology report of both breasts showing invasive ductal carcinoma Grade III (H and E, ×100)|
Click here to view
She received six cycles of adjuvant chemotherapy injection docetaxel, injection doxorubicin, and injection cyclophosphamide (TAC) followed by locoregional RT to the right chest wall [Figure 4] in view of node positivity to a dose of 45 Gray (Gy) in 20 fractions by three-dimensional conformal RT technique. She tolerated treatment well and is presently on regular follow-up without any evidence of local recurrence or distant metastasis. Patient and her daughters were advised BRACA mutation testing, but they have been noncompliant till now.
|Figure 4: Patient during her radiotherapy session showing bilateral mastectomy scar and radiation markings right breast|
Click here to view
| Discussion|| |
Bilateral breast carcinomas are very rare constituting 2-5% of all breast malignancies  while triple negative bilateral carcinomas are still rarer. About 2-11% breast cancer patients will develop cancer in the opposite breast in their lifetime with an incidence rate of contralateral breast cancer varying from four to eight per 1000 person-years. An infiltrative lobular carcinoma is more prone for bilaterality and multicentricity as compared to infiltrative ductal carcinoma. Bilateral tumors can be either synchronous or metachronous.
Synchronous lesions are identified within 6 months of the primary tumor with an incidence of 0.2-2% while metachronous lesions appear after 6 months with an incidence of 5-6%. As compared to unilateral lesions, bilateral carcinomas have a worse prognosis in view of lower disease free interval and overall survival with a high propensity for distant metastasis. Similarly synchronous carcinomas are known to have a worse prognosis as compared to metachronous lesions.
To know whether the contralateral breast lesion is a second primary or metastasis, Chaudary et al . in 1984 postulated certain criteria like a contralateral tumor with in situ changes, histologically different from the initial lesion, histological differentiation greater than first, no evidence of local, regional, or distant metastases from early cancer. In general, the contralateral tumor is considered a synchronous second primary in the absence of systemic metastasis. In our case, with simultaneous appearance and absence of distant metastasis even with identical histology, the diagnosis of synchronous carcinoma was thought of.
The comparative genomic hybridization technique was devised in the 1990s to investigate the clonality of bilateral breast cancer. Synchronous carcinomas are considered biologically similar compared to metachronous lesions in view of higher concordance of histopathological similarity of 93% and 53% respectively, higher tumor-node-metastasis stage, higher hormone receptor, and HER 2 expression. This implies that treatment strategies for synchronous cancers could be same while metachronous cancers could be treated on a case to case basis.
Breast carcinoma is an aggressive disease with patients developing contralateral carcinoma, and such manifestation is uncommon though not unusual in the present scenario of highly advanced diagnostic modalities, definitive, and adjuvant treatments which has increased the life span of a patient where the bilateral state can manifest. This also implies that the patient harbors this risk during their entire lifetime which is further enhanced by the heterogenous nature of the breast disease which makes it difficult to identify the risk factors and assess the curative modality.
Without a known etiology of bilateral breast carcinoma, there are certain known risk factors such as familial or hereditary breast cancer, young age, nulliparity, lobular carcinoma, multicentricity, and prior radiation exposure. The presence of tumor suppressor genes BRACA 1/2 mutation in 5-10% women with breast carcinoma subjects them to 40% risk of developing a contralateral primary. BRACA mutations are more frequent in metachronous lesions as compared to synchronous lesions where environmental carcinogens are more influential.
BRACA 1 is associated with triple negative carcinomas which do not respond to hormonal therapy or trastuzumab while BRACA 2 is associated with postmenopausal women. In our case, we were not able to determine the BRACA mutation status because of noncompliance of the patient. The cancer risk caused by BRACA 1 and BRACA 2 mutations are inherited in a dominant pattern as these mutated genes can be inherited from either parent and are therefore classified as hereditary mutations.
BRACA mutation should therefore be tested in first, second or third degree relatives with breast cancer diagnosed at 50 years or less, bilateral or multiple breast cancers, triple negative breast cancer, two or more relatives with breast cancer with one under 50 years age, three or more relatives with breast cancer at any age, previous BRACA mutation in family and those with ovarian cancer. Prophylactic or preventive therapies with surgery or medications are known to decrease cancer risk in females with a high risk of BRACA mutation with no proven role of prophylactic RT. Prophylactic surgery techniques are a simple mastectomy, skin sparing mastectomy, nipple sparing mastectomy, subcutaneous mastectomy, areola sparing mastectomy and nerve sparing mastectomy. Prophylactic tamoxifen, a selective ER modulator is found to be effective in women not desirous for surgery.
About 10-20% breast cancers are triple negative which test negative for both hormone receptors (ER/PR) and HER 2. Regarding triple negative bilateral breast carcinomas, only Senkus et al . reported an incidence of 5% in synchronous and 16% in metachronous lesions. They tend to be more aggressive, more likely to spread beyond the breasts, higher recurrence rate, and higher grade than other types. Triple-negative cancers are thought to originate from basal-like cell types, a new subtype of breast cancer cells. They do not respond to therapies such as tamoxifen, anastrozole, exemestane, letrozole, fulvestrant, trastuzumab, and lapatinib. However, they are treated with a multimodality approach of surgery, chemotherapy, and RT. Mastectomy instead of lumpectomy is employed in view of aggressive nature of the disease. Chemotherapy is sometimes considered as neo-adjuvant or adjuvant setting while RT remains the mainstay of local adjuvant therapy. There are on-going clinical trials regarding targeted therapies like poly adenosine diphosphate ribose polymerase inhibitors, vascular endothelial growth factor inhibitors and epidermal growth factor receptor (EGFR) inhibitors, more effective against triple-negative breast cancers, which unlike chemotherapy and RT, target a specific process or channel in the biochemical pathway of the cancer cells.
Presently, there are no definite treatment algorithms for bilateral breast carcinomas. Patients are treated with bilateral MRM in the case of invasive carcinoma while no definite role of breast conservative surgery or a lumpectomy has been established so far. As in our case, a multimodality treatment is generally used as in cases of unilateral carcinomas with optimal results. About 20-30% of individuals recur after mastectomy and radiation to the operated site along with lymph nodal stations reduces this risk by 70%. In the present scenario of breast cancer treatment, there is no large series to compare RT and mastectomy as the definite approach and until such time RT continues to play an adjuvant and palliative role. About the novel concept of nonmedical therapy in BRACA carriers at risk of developing unilateral or bilateral breast carcinoma, no lifestyle modifications like dietary change or food supplements, exercise or maintaining an ideal body weight or bearing a first child at a younger age or prolonged breastfeeding have proven to be of any benefit. The only measure which has been proved to have a significant benefit of preventing breast carcinoma is a reduction of alcohol intake to one drink per day.
The purpose of reporting this sporadic and unusual case of triple negative synchronous bilateral IDC of the breast was to highlight the therapeutic challenge we faced during the entire clinical course, thus recommending an extensive screening protocol for women with high risk of contralateral breast carcinoma adjusted according individual and hereditary factors. Not only oncologists at Tertiary Care Centres but any primary health care provider at the primary care level and any general practitioner should emphasize on breast self-examination to detect any breast lump as early as possible along with screening clinical breast examination. Screening magnetic resonance imaging of breasts starting at 20 and 30 years of age once a year and mammography after 50 years should be stressed upon. Alternative screening modalities are breast USG, computed tomography scans, PET scans, scintimammography, thermography, elastography, ductal lavage, biomarkers such as ER, PR, HER 2, vimentin, cytokeratin 5/6, E-cadherin, EGFR status and biopsies from suspicious areas. BRACA mutation testing is of utmost importance in high-risk population as stated above. Genetic counselling is also recommended to inform and educate candidates at risk about the meaning of the mutation tests, the benefits, the limitations, the prophylactic remedies if the result is positive and also for emotional support of the individual. These screening methods will not only help to detect any suspicious lesion early before it progresses to malignancy and guide prompt implementation of appropriate treatment strategies.
We would like to thank the patient for allowing us to publish the case report and use the images taken during her stay in hospital.
Financial support and sponsorship
Conflicts of interest
There are no conflicts of interest.
| References|| |
Tuttle TM, Douglas Y. Bilateral breast cancer. In: Singletary SE, Robb GL, Hortobagyi GN, editors. Advanced Therapy of Breast disease. 2nd
ed. USA: B C Decker Inc.; 2004. p. 629-30.
Chen Y, Thompson W, Semenciw R, Mao Y. Epidemiology of contralateral breast cancer. Cancer Epidemiol Biomarkers Prev 1999;8:855-61.
Carmichael AR, Bendall S, Lockerbie L, Prescott R, Bates T. The long-term outcome of synchronous bilateral breast cancer is worse than metachronous or unilateral tumours. Eur J Surg Oncol 2002;28:388-91.
Kollias J, Ellis IO, Elston CW, Blamey RW. Prognostic significance of synchronous and metachronous bilateral breast cancer. World J Surg 2001;25:1117-24.
Kheirelseid EA, Jumustafa H, Miller N, Curran C, Sweeney K, Malone C, et al.
Bilateral breast cancer: Analysis of incidence, outcome, survival and disease characteristics. Breast Cancer Res Treat 2011;126:131-40.
Chaudary MA, Millis RR, Hoskins EO, Halder M, Bulbrook RD, Cuzick J, et al.
Bilateral primary breast cancer: A prospective study of disease incidence. Br J Surg 1984;71:711-4.
Gong SJ, Rha SY, Jeung HC, Roh JK, Yang WI, Chung HC. Bilateral breast cancer: Differential diagnosis using histological and biological parameters. Jpn J Clin Oncol 2007;37:487-92.
Weitzel JN, Lagos VI, Cullinane CA, Gambol PJ, Culver JO, Blazer KR, et al.
Limited family structure and BRCA gene mutation status in single cases of breast cancer. JAMA 2007;297:2587-95.
Senkus E, Szade J, Pieczynska B, Zaczek A, Pikiel J, Sosinska MC, et al
. Are synchronous and metachronous bilateral cancers different? An immunohistochemical analysis aimed at intrinsic tumor phenotype. Int J Clin Exp Pathol 2014;7:353-63.
Morris JL, Gordon OK. Positive Results: Making the Best Decisions When you are at High Risk for Breast or Ovarian Cancer. Amherst, N.Y.: Prometheus Books; 2010.
[Figure 1], [Figure 2], [Figure 3], [Figure 4]