Back ground: Breast cancer is the most common cancer among women counting about 125 per 100000 per year new case in United States and about 1.4milion new cases worldwide. In the last twenty years early diagnosis, neoadjuvant and adjuvant systemic treatment that targeted to specific molecular targets have significantly reduced the mortality from breast cancer. Distant metastasis accounts for the vast majority of deaths in patients with cancer. Breast cancer exhibits a distinct metastatic pattern commonly involving bone, liver, lung, and brain. Breast cancer can be divided into different subtypes based on gene expression profiles, and different breast cancer subtypes show preference to distinct organ sites of metastasis.

Bilateral breast cancer (BBC) is rare and is associated with unfavorable prognosis. riple-negative breast cancer (TNBC) has been associated with a more aggressive histology, poorer prognosis, and no responsiveness to hormone therapy. It is imperative that cancer research identify factors that drive disparities and focus on prevention.

We report A case of metastatic bilateral breast cancers, A 58-year-old female presented with bilateral breast masses of 8-years duration. On examination. she had bilateral fungated breast masses, which were hard, mobile, and irregular. On the right side, there was skin tethering and palpable axillary lymph nodes. Ultrasound examination showed a heterogeneous, irregular, ill-defined, mass-like lesion, seen in the upper outer quadrant of the right breast along with a hypoechoic. irregular mass 12*13mm in the upper outer quadrant of the left breast. FNA showed bilateral invasive ductal carcinoma. Right axillary lymph nodes were positive for adenocarcinoma. She received 4 sessions of NACT which was followed by right-side mastectomy with axillary lymph node dissection and left-side mastectomy with sentinel lymph node biopsy

Breast cancer is the most commonly diagnosed cancer and ranks the fifth cause of cancer death among females worldwide, with an estimated 2.3 million new cases (11.7%) and 685 thousand deaths (6.9%) in 2020[1]. It has become the major reason for mortality in women in the age group of 40 to 59 years, the premenopausal women based in Central, America, Africa, and South America are more prone to be affected with breast cancer [31]

The occurrence of bilateral breast cancer is increasing nowadays with reported incidence ranging in between 1.4%-12%. [2,3]. however, in recent literature, patients with BBC showed significantly worse distant relapse -freesurfival as coped to those with unliteral breast cancer as distant metastasis were frequently reported in patients with BBC. [3,4] BC can metastasize to several organs, the most frequent metastatic sites include bone, lungs, liver and skin [5] The incidence of bilateral breast cancer has been reported to be 4.4% (2.1% synchronous and 2.3% metachronous.[6].

Patient information

A 51-year-old female presented with bilateral breast masses for 5-yeras duration. She was G1P1, lactated for 2 years, she is divorced. She had regular menstrual cycles in the past. She didn't have any chronic disease. She had bilateral breast mass but she neglected this due to social sham and financial status of patient.

On clinical examination, there was bilateral palpable breast masses, hard, mobile and irregular and crusted. On the right side, there was skin tethering and palpable axillary lymph nodes.

Diagnostic assessment on October10,2022 Ct scan chest and abdomen and pelvic there was bilateral areola-nipple proliferative soft tissue lesion with diffuse skin thicking and underlying asymmetrical breasts parenchymal infiltrative hyper density. More evident in left side with deep calcification and shrinking left breast size.

An ill-defined soft tissue density in left axilla encasing vessels.lymphiod process.

Focal chest wall muscle enhancement in anterior aspect of teras minor and latissimus dorsi muscles is seen.

Bilateral pleural effusion.moderat  in left side,nopulmonary or mediastinal lesion

Solitary hepatic benign looking focal cystic lesion  and splenic  small focal lesion .

Multiple uterine  masses  of variable size (subserous and intra mural degenerated fibroids)

Diffuse abdominal wall subcutantanouse fat edematous congestion.

 *on 25May2022 left breast mass true cut biopsy report show invasive ductal carcinoma(N

* on6 July2022   Immunohistochemistry Estrogen  reports 0/8                                 

 Progesterone reports 0/8

HER-2/neu protein 0 negative FISH is not required. Therapeutic intervention 

**on 6,July2022 She received 4 cycles AC then 4cycles finish in  9Augest,2022

Evaluation done by Ct scan   chest and abdominopelvic 25/8/2022 show: mild, bilateral breast edema  with left  side  areoleo-nipple thiching ,  bilateral pleural effusion, massive in left side ,minimal ascites ,tiny cystic lesion in liver 1.5cm between  segment V/VI .pedunculated  myomas up  to 3.5x3.7cm,diffuse abdominal wall and sub cutaneous fat edema. In comparing with CT report date 10/5/2022 there is mild increase in the pleural effusion  with nearly decreased rest of the finding  and no deposits in the axilla or muscles as it were previously reported (.figure1)

                                                                        Figure 1(A+B): Appearance of the bilateral breast cancers at pre- chemotherapy 2/6/2022

Patient Taxol given weekly for 12weeks start in 30/8/2022 finished in 9/11/2022. ( Figure 2+3)

                                              Figure 2(A+B): Appearance of bilateral breast cancers post 4cycles chemotherapy EC protocol (9/8/2022)

                              Figur 3: Appearance of bilateral breast cancer post 9 weeks monotherapy with paclitaxel (9/11/2022).

Patient complain lower limbe oedema, dopllar US done no signs of DVT, tumur marker : CA125:43.3,CA15.3:45,CEA:4.87. Advice new line chemotherapy with gemctabin+ Xeloda for three cycles than evualtion done by chest and abdomenand pelvic Ct scan in 19/3/2023 show regression course regarding  bilateral  plural effusion .stable  regareding right  adnexal  and spleeinc and hepatic  lesion.no bony lesion.complet resulation. of LLedoma but patient can not tolerated with gemctabin side effect tumur marker: CEA 2.5, CA15.3:26.5, CA:45. (figure5)

                                                               Figure 5: post 3 cycles gemcitabine + xeloda 19/3/2023 >>> resolve breast mass in left  breast

Xeloda tab advice  to continue for 3cycles ,patient tolarted and advice more three cycles + hormonal therapy  Exemestan 25mg tab 13/6/2023.

Evualtion done in 26/9/2023show good respone, mild left side plural effusion, no ovarin mass. Tumur marker CEA :3, CA19.9:24.9, CA15.3:20.69, CA125:7.9. figure 6

                                                                                  Figure 6: post 6 cycles xeolda (capecitabine) 26/9/2023; good respond

Advice continue three cycles  xeloda and continue  with hormonal therapy Exemestan  (2/10/2023) ( figure7) 

Figure 7: Post-10 cycles xeloda 2/10/2023

2.5. Follow up

*on5 Februy,2024: chest and abdomen  CT scan show: Left beast  not seen  with clear surgical bed and free both axilla.

Left lung  upper lobe well-defined enhanced pleural  based soft tissue  nodule 17x28mm.

No significant  changes regarding  hepatic cystic lesion ,uterine and splenic  lesion  in compare with study at 26/9/2023 current study show  stable course .

•               On 26July,2024: CT scan of chest with contrast show: clear surgical  bed ,no local recurrence, sub -pleural nodule 25x13mm seen at level  of lingula ,at pervious exam measured 28x15mm, relative decreased  size of lesion in comparison with previous exam case is with relative  decreased  mass size.

Ct scan  of abdomen and pelvic  with contrast show : low attenuation, non hancing  hepatic  cyst 20x14mm.in comparison  with last study case in 5/2/2024  is with  stationary course..

Tumor  marker: CA 35.75(0.00-39)

CA125 13.39(0.001-35)

CA15.326.36(0.00-25).advice her to  fellow up and continue  on hormonal therapy Anastrazol 1mg po daily .

On 20Septamber 2024: come patient  for follow up ,complain  new skin nodules(figure 10) 

Advice : continue  xeloda+ Armadax   protocol

Post-chemotherapy  period . She was followed up for two year. 

                                                                                                   Figure 10: skin nodules in bilateral breast cancer

Patient condition improve skin nodules and advice to continues on Capecitabine and Anastrozole

                                                                                                            Figur 8: post 13 cycles xeloda 12/12/2023 

                    Figure 9: On hormonal therapy 16/4/2024 complete resolution of left breast mass+ right breast shows good response           

Breast cancer is the most common site-specific cancer in women and is the leading cause of death from cancer for women aged 20–59 years. It accounts for 26% of all newly diagnosed cancers in females and is responsible for 15% of the cancer-related deaths in women [32].

 Nevertheless, the incidence of breast cancer in Western countries is about sixfold higher than the developing countries of Africa and Asia owing to demographic factors such as longer life expectancy, better and early reporting of cases and easy access to healthcare [9]. Bilateral breast carcinomas are very rare. They form 2–5% of all breast malignancies. About 2–11% of breast cancer patients develop cancer in the opposite breast in their lifetime with an incidence rate varying from 4 to 8 per 1000 people per year. BRCA1 and BRCA2 mutation carriers have an annual risk of 2%–6% of developing a second primary breast cancer[33]. In December 2013, the U.S. Preventive Services Task Force recommended risk assessment, genetic counseling, and genetic testing for BRCA-related cancer in those patients who may have an increased likelihood of a BRCA mutation. In addition to other factors, this included those patients with bilateral breast cancer [34].

Family history of breast cancer is a risk factor for the development of unilateral breast carcinoma; it wouldn't be an unreasonable hypothesis to think that it could be a risk factor for bilateral breast carcinoma. Some authors have submitted data supporting this hypothesis [7] . The risk factors associated with bilateral occurrence include: a positive family history of breast cancer in a first-degree relative, young age at diagnosis of primary breast cancer, histologically diagnosed invasive lobular carcinoma of the initial breast mass lesion, multicentricity and previous history of exposure to ionizing radiation [8].Triple-negative breast cancer (TNBC) has been found to account for approximately 15% of all breast cancer cases, and is associated with aggressive histology, poorer prognosis, shorter survival, and unresponsiveness to usual hormone therapy[10].TNBC disproportionally affects younger women, women of African American descent, and women with Breast Cancer gene 1 (BRCA 1) mutation diagnoses [11-15]. The current diagnostic method takes multiple steps, is expensive, and does not diagnose TNBC promptly. TNBC is currently diagnosed in higher stages, with 12% of women diagnosed at stage 1, 11% diagnosed at stage 2, 52% diagnosed at stage 3, and 25% diagnosed at stage 4{16}.. Despite the more aggressive clinical behavior of TNBCs, several studies have now demonstrated that patients with these cancers more frequently evolve to pathologic complete response following neoadjuvant chemotherapy [17].In the metastatic setting, however, TNBCs remain lethal despite the recent US Food and Drug Administration (FDA) approvals of different modalities of therapeutic agents for patients with this disease[18-19].Treatment for TNBC depends on different factors, such as the stage and the grade of the cancer. It is usually a combination of surgery, radiotherapy and chemotherapy. Unlike most other types of BC, TNBC does not express estrogen, progesterone and HER2 receptors. Therefore, hormone therapy is largely ineffective for treatment purposes. Nevertheless, TNBC often responds very well to chemotherapy. [20-22]. Neoadjuvant chemotherapy is the primary systemic treatment for TNBC, which improves pathologic complete remission, increasing surgical success, reducing the extent of surgery, and allowing assessment of treatment response[27].

Anthracyclines and taxanes are the main chemotherapeutic regimens against TNBC. Anthracyclines, such as doxorubicin, are molecules that inhibit topoisomerase II, blocking DNA replication and transcription and, consequently, arresting the cell cycle. Taxanes (e.g., paclitaxel and docetaxel) are antimitotic agents that inhibit cell division by affecting the stabilization of microtubules. Platinum-based compounds, such as carboplatin and cisplatin, interlink DNA strands, causing them to break and leading to cell apoptosis. This is particularly beneficial in the case of tumors that carry BRCA gene mutations, with underlying impaired DNA repairing mechanisms, and prevalent among TNBC patients. Other drugs, such as cyclophosphamide (causing DNA damage), fluorouracil, and capecitabine (blocking DNA synthesis) have also been used, particularly in combination or in sequential regimens with anthracyclines and/or taxanes or when the latter are contraindicated [23] However, TNBCs lack the benefit resulting from the use of targeted or hormonal systemic therapies in other subtypes. In this regard, a deeper knowledge of the molecular characteristics of TNBCs paved the way for the development of novel targeted therapeutics and patient stratification.[24]. Chemoresistance is a growing concern in TNBC therapy, with about 30–50% of patients undergoing neoadjuvant therapy evolving to resistant recurrences, resulting in poor outcomes [25]. Mechanisms of resistance arise when tumor cells are exposed to cytotoxic agents, as a means of maintaining their viability. Some of these mechanisms have been demonstrated for TNBC standard therapies, and strategies to overcome them have been proposed [26] Extended adjuvant metronomic capecitabine is well tolerated with good patient compliance. Due to our small sample size, these results need to be compared in a study with a control arm, a larger sample as well as longer follow-up. The need for higher doses of capecitabine can be evaluated when the results of current ongoing trials are available [28].In recent years, some studies about capecitabine for therapy were also carried out in (neo)adjuvant therapy. They showed that addition of capecitabine to TNBC adjuvant treatment after anthracycline and paclitaxel combined adjuvant chemotherapy. shows that the DFS and OS have not been improved in addition, four cycles of sequential capecitabine after standard anthracycline and taxane regimens containing adjuvant chemotherapy, but DFS has a trend of improvement, which may be caused by the insufficient treatment cycles of capecitabine only four cycles, the insufficient number of cases, or the insufficient follow-up [29]  one study show Androgen receptor (AR) status might be used to identify a subgroup of patients with ER negative tumours benefitting from adjuvant tamoxifen treatment. We interpret this to mean that patients with ER− tumors may have their tumors tested for AR and could be candidates for tamoxifen therapy. We also identified a subgroup of patients with TNBC who had AR+ tumors that may be treated with tamoxifen to improve outcome. These hypotheses generating observations need confirmation by further studies with larger number of ER− and TNBC patients in prospective cohorts [30].

Although bilateral breast cancer is not frequent, MC breast cancer is different from SC breast cancer by having more advanced grade, stage, less ER expression, more frequent rates of local relapse and distant metastasis and better response to chemotherapy in case of relapse/metastasis. Bilateral carcinoma of the breast is very rare. Microscopically, the findings usually reveal infiltrative ductal carcinoma. The treatment of choice is bilateral modified radical mastectomy. TNBC is merely an operational term that stemmed from the fact that, in the mid-2000s, the only systemic therapy available for patients with ER-, PR-, and HER2-negative disease was chemotherapy.