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 Table of Contents  
CASE REPORT
Year : 2018  |  Volume : 8  |  Issue : 4  |  Page : 176-179

Long-term survival in a patient with bilateral metachronous triple negative breast cancer: A case report and literature review


Department of Radiotherapy and Oncology, Ahmadu Bello University Teaching Hospital, Zaria, Nigeria

Date of Submission13-Oct-2019
Date of Acceptance19-Dec-2019
Date of Web Publication10-Feb-2020

Correspondence Address:
Dr. Ismail Hadi Zubairu
Department of Radiotherapy and Oncology, Ahmadu Bello University Teaching Hospital Zaria
Nigeria
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Source of Support: None, Conflict of Interest: None


DOI: 10.4103/ais.ais_19_19

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  Abstract 


The incidence of bilateral metachronous breast cancer is rare in our environment. We report the rare case of a 44-year-old woman who has survived for 12 years after she was first diagnosed with stage 3B medullary right breast cancer. She had a positive family history of breast cancer in her paternal grandmother. She was treated with mastectomy and axillary clearance, six cycles of combination chemotherapy and external beam radiotherapy. She was also placed on tamoxifen. She developed a second primary breast cancer in the contralateral breast; triple negative, 10 years after her first diagnosis. She was treated with modified radical mastectomy and six cycles of Docetaxel with excellent response. She completed her chemotherapy about 2 years ago and has been on follow-up with no evidence of loco-regional recurrence.

Keywords: Bilateral breast cancer, cancer survival, metachronous cancer


How to cite this article:
Zubairu IH, Adewuyi SA. Long-term survival in a patient with bilateral metachronous triple negative breast cancer: A case report and literature review. Arch Int Surg 2018;8:176-9

How to cite this URL:
Zubairu IH, Adewuyi SA. Long-term survival in a patient with bilateral metachronous triple negative breast cancer: A case report and literature review. Arch Int Surg [serial online] 2018 [cited 2020 Apr 1];8:176-9. Available from: http://www.archintsurg.org/text.asp?2018/8/4/176/278023




  Introduction Top


The incidence of bilateral breast cancer is increasing globally as a result of patients surviving for longer years.[1] Improvements in chemotherapy, hormonal therapy, and radiotherapy have significantly increased the overall survival of patients with breast cancer. Breast cancer is a major public health problem for women globally,[1] and women diagnosed with breast cancer are at increased risk of developing contralateral breast tumor, two to six times greater than developing a first breast cancer in the general population.[2] Metachronous, bilateral breast cancer is a rare entity accounting for 3–7% of all breast cancer cases.[1]

Here we present the case of a 44-year-old woman who developed a new primary tumor (NPT), invasive ductal carcinoma in the left breast 10 years after completing treatment for a primary breast cancer, medullary breast cancer, in the right. She has completed treatment for the second breast cancer, and is in her second year follow-up with no evidence of disease recurrence. We describe the diagnostic and therapeutic approach of her management, along with existing literature.


  Case Report Top


Mrs. HB, a 44-year-old lawyer, first presented to our radiotherapy clinic in 2006, when she was 32 years old, on referral from another hospital where she was diagnosed with right breast cancer, six months earlier. She was diagnosed clinically stage 3B. She had a positive family history of breast cancer in her paternal grandmother, which was the only positive risk factor. A simple mastectomy with right axillary lymph node dissection was done for her, and histology report from mastectomy specimen showed medullary breast cancer with involvement of the resection margins and dissected lymph nodes. Immunohistochemistry testing wasn't done because the facilities for this service weren't available at the time. This was followed by 4 cycles of chemotherapy using VAC-P regimen (Vincristine, Adriamycin, Cyclophosphamide and Cisplatin) and daily tamoxifen 20 mg. She was referred to our facility for external beam radiotherapy.

In our facility we obtained a detailed clinical history which was essentially the same as the information contained in the referral letter. Physical examination revealed a well-preserved young lady with a Karnofsky Performance Score of about 90%. Chest wall inspection revealed absent right breast with keloid formation along the surgical scar. There were no supraclavicular or axillary lymph nodes palpable, bilaterally. Systemic examination was not contributory.

Laboratory investigations conducted including complete blood count (CBC), renal function tests, liver function tests, chest X-ray, and abdomino-pelvic ultrasound scan were all normal.

We discovered during discussion with the patient that the doses of chemotherapy previously given were suboptimal, so we started her on 2nd line chemotherapy using CAF regimen (cyclophosphamide 600 mg/m2, adriamycin 60 mg/m2, and 5-fluorouracil 600 mg/m2), and she received six cycles. She then had external beam radiotherapy to the right chest wall, supraclavicular fossa and axilla using four-field technique. She received a total of 50 Gy in 25 fractions over 5 weeks with excellent response to treatment.

She was subsequently discharged home to be seen on follow-up every 3 months for the first 2 years and then every six months for close monitoring. She was regular with her follow-up visits, and her hormonal treatment was changed from tamoxifen to exemestane after 5 years. She used exemestane for 2 years and then reverted back to tamoxifen, which she has continued to use up till her last follow-up visit.

Ten years after her diagnosis, during a follow-up visit, she was discovered to have a lump in the central region of her left breast, just below the nipple. A mammogram was requested for and the result was BIRADS 3. A consult was sent to the surgeons for a biopsy, and the histology report came out as invasive ductal carcinoma. She subsequently had modified radical mastectomy with left axilla lymph node clearance. Histology report of mastectomy specimen showed invasive ductal carcinoma (NST) with involvement of the lymph nodes; both the nipple and resection margins were free. Immunohistochemistry revealed that the tumor was ER negative, PR negative, and Her2neu negative. The patient was worked up for 3rd line chemotherapy and received six cycles of docetaxel 80 mg/m2.

She had developed mild lymphedema of the left upper limb following surgery, and this made us wary of irradiating the supraclavicular fossa and axilla. We requested for a high-resolution CT-scan to ascertain the status of both regions. They were both determined to be lymph node free. We decided to withhold external beam radiotherapy to avoid worsening lymphedema and the attendant complications since both resection margins were free as well as the supraclavicular fossa and axillae. She completed her chemotherapy about 2 years ago and has been on close follow-up since then with no evidence of loco-regional recurrence.


  Discussion Top


The patient we have presented had the typical characteristics of patients presenting with medullary breast cancer which was her first diagnosis. She was young; 32, and had a strong family history of breast cancer. Medullary breast cancer is a rare entity accounting for about 3–5% of all breast cancers.[3] The average age at presentation from literature is 45–52 years;[4] although ours presented earlier. Medullary cancers are almost always triple negative.[4] Unfortunately, many centers in Nigeria were unequipped to perform immunohistochemistry testing at the time she was diagnosed.

Invasive ductal carcinoma (IDC) on the other hand is the most common histological type of invasive breast cancer accounting for 70–80% of all breast cancer cases.[5] It also has the worst prognosis.[5],[6] The average age at presentation is 45–52 years, which corresponds to the age at which our patient presented with IDC.

Treatment is generally based on a multidisciplinary approach and involves primary tumor surgery, which could either be a Breast Conserving Surgery (BCS) or mastectomy, adjuvant chemotherapy and radiotherapy, and hormonal treatment if indicated. Our patient had a mastectomy done, received chemotherapy, radiotherapy, and hormonal therapy.

A number of randomized prospective studies have shown that mastectomy and breast-conserving treatment in IDC have similar outcomes in terms of overall survival, disease-free survival, and long-term disease-free survival.[7],[8] The risk of a second breast cancer is the same whether the patient previously had a mastectomy or Breast Conserving Treatment (BCT). And with BCT, there is no difference in the risk of developing a secondary breast cancer either in the contralateral breast or in the same breast. Unlike disease recurrence (which usually occurs within 12 to 30 months), second primary breast cancer often occurs after the first 36 months, with an average range from 34 to 60 months, requiring a long-term follow-up.[9] In this case, our patient presented with a second primary breast cancer in the contralateral breast 120 months after the first diagnosis. Adherence to the follow-up schedule was important in diagnosing the second breast cancer early. Furthermore, our case is not a case of recurrence because typically, true recurrences (TR) show a histological pattern that is consistent with the re-growth of malignant cells not removed by surgery or not killed by radiotherapy.[7] On the other hand, new primary tumors (NPTs) are de novo cases of malignancies arising from mammary epithelial cells of the residual breast tissue[7],[10] which differ from the initial breast tumor in terms of histological type, location, and DNA cytometry.[11] In our patient, the second tumor differed from the first in at least two aspects, namely, histology and location.

TR generally has a poor prognosis in terms of survival rates and development of metastases.[11] In contrast, patients with NPT generally have a more favorable prognosis, and therapeutic decisions concerning systemic therapy should be similar to those in patients with de novo breast cancer, according to the equivalent stage.[12]

In patients who have an increased risk of developing contralateral breast cancer either by genetic disposition or some other factor, some studies have shown that patients with NPT benefit from adjuvant tamoxifen if indicated, because it reduces the incidence of contralateral and ipsilateral disease recurrence.[12] In a retrospective study conducted by Bouchardy et al. about second primary contra lateral breast cancers, they found that women with ER-positive first tumors have a decreased risk of second breast cancer occurrence [standardized incidence ratio (SIR): 0.67; 95% confidence interval (CI), 0.48–0.90], whereas patients with ER-negative primary tumors have an increased risk limited to ER-negative second tumors (SIR: 7.94; 95% CI, 3.81–14.60).[9] Patients with positive family history had a 10-fold higher risk of ER-negative second tumors which increased to nearly 50-fold when the first tumor was ER negative. So, the risk of second ER-negative breast cancer is increased exponentially after a first ER-negative tumor, particularly in women with strong family history.[9] We are unable to make these comparisons in our case because her first breast cancer was not tested for hormone receptor status. However, she did have a strong positive family history.

Several studies have shown that there is no significant difference in survival for patients with unilateral compared to all bilateral breast cancers[13] or compared to metachronous breast cancer diagnosed after 5 years.[14] Synchronous breast cancer, however, has been found to be associated with poorer survival compared to both metachronous breast cancer and unilateral breast cancer.[2],[14] A study carried out by Alejandra M. Garcia et al. shows that the 5 year survival for unilateral cancers, metachronous cancers and synchronous cancers were 85.9%, 94.6%, and 63.3%, respectively, while 15 year survival rates were 65.5%, 52.3%, and 37.2%, respectively.[14] They also found that the incidence of bilateral breast cancers is low, and that survival in patients with metachronous breast cancer diagnosed after 5 years is similar to those with unilateral cancer.

The case we have reported has a number of factors, evidenced by literature, which favor long survival. First, her first primary breast cancer was medullary histology, the second primary breast cancer although IDC, was diagnosed 10 years after her first diagnosis. Metachronous tumors have been found to have better survival outcomes than synchronous tumors. The patient was also placed on tamoxifen, which has been found to reduce the incidence of disease recurrence.


  Conclusion Top


The case presented gives supporting evidence to previous research findings that secondary NPT are more common in women previously diagnosed with breast cancer. It is shown that with conscientious management and regular follow-up, it is possible to identify metachronous cancers in previously treated patients and commence treatment early.

Financial support and sponsorship

The authors wish to declare that no support was received in writing this case report.

Conflicts of interest

There are no conflicts of interest.



 
  References Top

1.
Ferlay J, Autier P, Boniol M, Heanue M, Colombet M, Boyle P. Estimates of the cancer incidence and mortality in Europe in 2006. Ann Oncol 2007;18:581-92.  Back to cited text no. 1
    
2.
Heron DE1, Komarnicky LT, Hyslop T, Schwartz GF, Mansfield CM. Bilateral breast carcinoma: Risk factors and outcomes for patients with synchronous and metachronous disease. Cancer 2000;88:2739-50.  Back to cited text no. 2
    
3.
Kleer CG. Carcinoma of the breast with medullary-like features: Diagnostic challenges and relationship with BRCA1 and EZH2 functions. Arch Pathol Lab Med 2009;133:1822-5.  Back to cited text no. 3
    
4.
Li CI, Uribe DJ, Daling JR. Clinical characteristics of different histologic types of breast cancer. Br J Cancer 2005;93:1046-52.  Back to cited text no. 4
    
5.
Elston CW, Ellis IO. Pathological prognostic factors in breast cancer. I. The value of histological grade in breast cancer: Experience from a large study with long-term follow-up. Histopathology 1991;19:403-10; Histopathology 2002;41:151-2.  Back to cited text no. 5
    
6.
Cao AY, He M, Huang L, Shao ZM, Di GH. Clinicopathologic characteristics at diagnosis and the survival of patients with medullary breast carcinoma in China: A comparison with infiltrating ductal carcinoma-not otherwise specified. World J Surg Oncol 2013;11:91.  Back to cited text no. 6
    
7.
Veronesi U, Cascinelli N, Mariani L, Greco M, Saccozzi R, Luini A, et al. Twenty-year follow-up of a randomized study comparing breast-conserving surgery with radical mastectomy for early breast cancer. N Engl J Med 2002;347:1227-32.  Back to cited text no. 7
    
8.
Fisher B, Anderson S, Bryant J, Margolese RG, Deutsch M, Fisher ER, et al. Twenty-year follow-up of a randomized trial comparing total mastectomy, lumpectomy, and lumpectomy plus irradiation for the treatment of invasive breast cancer. N Engl J Med 2002;347:1233-41.  Back to cited text no. 8
    
9.
Bouchardy C, Benhamou S, Fioretta G, Verkooijen HM, Chappuis PO, Neyroud-Caspar I, et al. Risk of second breast cancer according to estrogen receptor status and family history. Breast Cancer Res Treat 2011;127:233-41.  Back to cited text no. 9
    
10.
Komoike Y, Akiyama F, Iino Y, Ikeda T, Tanaka-Akashi S, Ohsumi S, et al. Analysis of ipsilateral breast tumor recurrences after breast-conserving treatment based on the classification of true recurrences and new primary tumors. Breast Cancer 2005;12:104-11.  Back to cited text no. 10
    
11.
Cuerda S, Ramírez N, Chara L, Cassinello J. Primary ipsilateral metachronous breast tumor: A case report. Case Rep Oncol 2012;5:580-5.  Back to cited text no. 11
    
12.
Dalberg K, Johansson H, Johansson U, Rutqvist LE. A randomized trial of long-term adjuvant tamoxifen plus postoperative radiation therapy versus radiation therapy alone for patients with early stage breast carcinoma treated with breast-conserving surgery. Stockholm Breast Cancer Study Group. Cancer 1998;82:2204-11.  Back to cited text no. 12
    
13.
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.  Back to cited text no. 13
    
14.
Vuoto HD, García AM, Candás GB, Zimmermann AG, Uriburu JL, Isetta JA, et al. Bilateral breast carcinoma: Clinical characteristics and its impact on survival. Breast J 2010;16:625-32.  Back to cited text no. 14
    




 

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Abstract
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