Diagnosis and treatment of metachronous multiple primary carcinoma: A case report and review of literature

Table 1 The treatment regimen

Date	Treatment management	Efficacy evaluation
December 2017 to April 2018	In December 2017, modified radical mastectomy for left breast cancer and 4 cycles of EC regimen chemotherapy from December 2017 to March 2018. In April 2018, 4 cycles of chemotherapy were administered using the docetaxel regimen	The therapeutic effect was evaluated as CR
June 2018 to May 2021	Radiotherapy for proliferative lesions with a PTV of 50 Gy/25 fractions for proliferative lesions in the lung posterior right upper lobe in August and tamoxifen endocrine therapy was taken after it. The patient continues to receive treatment with tamoxifen combined with leuprorelin in May 2021	The therapeutic effect was evaluated as CR
August 2023	Diagnosed as DLBCL. R-CHOP regimen chemotherapy was administered, consisting of rituximab 600 mg/day 1, cyclophosphamide 1200 mg/day 1, doxorubicin 80 mg/day 1, vincristine 2 mg/day 1, and prednisone 100 mg/day 1-5	The patient developed neutropenia and fever after chemotherapy and then the dose was adjusted
September 2023 to December 2023	R-CHOP chemotherapy rituximab 600 mg/day 1, cyclophosphamide 1000 mg/day 1, pirarubicin 70 mg/day 1, vincristine 2 mg/day 1, and prednisone 100 mg/day 1-5. After second cycle of R-CHOP chemotherapy, CT showed a significant reduction of lymph nodes in the abdominal aorta, bilateral iliac vessels and abdominal compared to before	The therapeutic effect was evaluated as PR
January 2024 to February 2024	In January 2024, the treatment was changed to rituximab 500 mg/day 0, etoposide 0.15 g/day 1-3, ifosfamide 8 g/day 2, carboplatin 0.5 g/day 2. Bone marrow suppression significantly occurred after chemotherapy. In February 2024, the chemotherapy dosage was adjusted to rituximab 600 mg/day 0, etoposide 0.15 g/day 1-2, 0.1 g/day 3, ifosfamide 65 g/day 2, and carboplatin 0.4 g/day 2	The CT in July showed a reduction in the abdominal tumor, and the therapeutic effect was evaluated as PR
April 2024 to August 2024	From April to June 2024, 4 cycles of chemotherapy using a combination of 600 mg zuberitamab and Gemox regimen. The patient developed grade III bone marrow suppression at last chemotherapy. The fifth round of chemotherapy which included 600 mg of zuberitamab and Gemox regimen and lenalidomide starting from July. Targeted combination chemotherapy was administered in August, specifically consisting of rituximab 600 mg/day, gemcitabine 12 g/day, oxaliplatin 120 mg/day q2w, lenalidomide chemotherapy has been used ever since	The therapeutic effect was evaluated as PR
November 2024 until now	Rituximab 600 mg/day, gemcitabine 1 g/day, oxaliplatin 120 mg/day 1 q2w in November 2024. Targeted therapy with zebitumumab 600 mg was be administered in January 2025	The therapeutic effect was evaluated as CR. Currently, the patient's condition remained stable

EC: Epirubicin + cyclophosphamide regimen chemotherapy; PTV: Planning target volume; CR: Complete response; DLBCL: Diffuse large B-cell lymphoma; R-CHOP: Rituximab, cyclophospha-mide, hydroxydaunorubicin, Oncovin (vincristine) and prednisolone; CT: Computed tomography.

Table 2 Reports of metachronous multiple primary carcinoma of breast cancer and non-Hodgkin lymphoma and treatment strategies

Year	Patient description	Primary carcinoma	Second primary malignancy	Follow up management	Ref.
1983	A 52-year-old premenopausal white woman	Breast carcinoma	Aggressive, large cell lymphoma of the ileum (occur to twelve years after diagnosis and five years after the start of chemotherapy)	Treated for breast carcinoma with postoperative adjuvant chest wall irradiation, followed four and seven years later with therapy to spinal ports for palliation of metastatic disease. For the next three and a half years, she received oral cyclophosphamide on a daily basis to a total of more than 110 g	[12]
1989	A 51-year-old woman	Malignant lymphoma of the breast	Scirrhous carcinoma (two years after the operation)	For primary carcinoma modified radical mastectomy (Patey's method), in combination with chemotherapy (Cyclophosphamide, Vincristine, Prednisolone). for scirrhous carcinoma performed a modified radical mastectomy (Auchincloss' method), followed by chemotherapy (Tegafur)	[13]
1990	A 53-year-old female	Breast cancer (1980)	Malignant lymphoma of diffuse, small cell type (lymphoplasmacytic) (1988)	Radical mastectomy, followed by irradiation was performed in 1980	[14]
2002	A 70-year-old woman	A history of non-Hodgkin’s lymphoma and melanoma	Moderately differentiated infiltrating ductal carcinoma	Underwent a right breast lumpectomy with right axillary lymph node dissection	[15]
2015	A 55-year-old Caucasian woman	Simultaneous ductal carcinoma in situ of the right breast, and follicular lymphoma involving an inguinal lymph node and the left breast	Multifocal ductal carcinoma of the left breast and reappearance of the lymphoma in the left axillary lymph nodes (2 years later)	The patient underwent local excision and radiotherapy for the ductal carcinoma in situ, while a watch and wait strategy was adopted for the lymphoma. Two years later, underwent bilateral mastectomy, left sentinel node biopsy, and chemotherapy	[16]
2021	A 58-year-old woman	Breast cancer	Malignant lymphoma and colon cancer (2 years later)	Maliqnant lymphoma and colon cancer that occurred during breast cancer treatment	[17]

Table 3 Reports of synchronous multiple primary carcinoma of breast cancer and non-Hodgkin lymphoma and treatment strategies

Year	Patient description	Primary carcinoma	Primary management	Second primary malignancy	Follow up management	Ref.
1998	An 87-year-old woman	Invasive lobular carcinoma of the breasts	Underwent breast conserving surgery with ipsilateral axillary lymph node dissection	Stage IV diffuse large B-cell lymphoma (REAL classification)	3 courses of combination chemotherapy, vincristine, cyclophosphamide, idarubicin and prednisolon (CIOP)	[18]
2004	A 53-year-old woman	Breast cancer	Complete axillary lymph-node dissection	Low grade lymphoma	Not mentioned	[19]
2006	A 63-year-old woman	Invasive, grade 1, ductal carcinoma	Radiotherapy to left breast and was started on tamoxifen. Chemotherapy with four courses of adriamycin, carmustine, cyclophosphamide, and melphalan	B cell lymphoma, with peripheral mantle cells	Chemotherapy with fludarabine and cyclophosphamide	[20]
	A 50-year-old woman	Grade 1 invasive ductal carcinoma	Mastectomy	B cell type non-Hodgkin’s lymphoma, mature, follicular (all follicular, grade 1)	Radiotherapy to the left breast and was started on tamoxifen (20 mg daily). Treated with six courses of chlorambucil and dexamethasone
	A 58-year-old woman	Ductal carcinoma in situ of the comedo type	Left mastectomy	Low grade follicular non-Hodgkin’s lymphoma	No systemic treatment
2008	A 50-year-old female	Infltratingductal carcinoma of mucinous type	Axillary lymph a node dissection. The patient refused further radiotherapy treatment for the breast carcinoma	Non-Hodgkin's lymphoma of axillary lymph nodes	Chemotherapy regimen for CLL (cyclophosphamide 300 mg and prednisolone 30 mg daily)	[21]
2010	74-year-old woman	Multicentric invasive ductal breast carcinoma	Modified radical right mastectomy with level 2 axillary lymph node dissection	SLL	Chemotherapy, radiation, traztuzumab and hormonal therapy	[22]
	74-year-old woman	Invasive lobular breast carcinoma	Wide local excision and sentinel node biopsy	Low-grade B cell lymphoma	6 weeks of adjuvant radiotherapy followed by an aromatase inhibitor
	79-year-old woman	Breast cancer	Modified radical right mastectomy with axillary mass excised in continuity with the whole breast	Classical Hodgkin lymphoma	Local irradiation was chosen as initial treatment
	54-year-old woman	Grade 2, invasive ductal carcinoma	Wide local excision and axillary node dissection	Small lymphocytic B cell lymphoma	The decision was made to treat the lymphoma as a priority; this patient also required radiation treatment to the breast and axilla as well as further chemotherapy for stage IIA breast carcinoma followed by hormonal treatment
2010	A 52-year-old woman	Invasive ductal carcinoma, grade 2 of 3 (moderately differentiated)	Right total mastectomy and right axillary node dissection	Stage 1A follicular lymphoma	An adjuvant chemotherapy regimen, which entailed four cycles of dose dense doxorubicin (60 mg/m2) and cyclophosphamide (600 mg/m2), followed by dose dense paclitaxel	[23]
2011	A 47-year-old female	Ductal car cinoma right breast	Modified radical mastectomy of right breast	B-cell non-Hodgkin lymphoma	Not mentioned	[24]
2012	A 72-year-old Japanese woman	Breast tumor	Surgical resection for the breast tumor	IVLBCL	7 courses of R-CHOP (rituximab, cyclophosphamide, doxorubicin, vincristine, and prednisolone) at 3-week intervals	[25]
2014	A 51-year-old woman	Invasive ductal carcinoma (grade III)	Left modified radical mastectomy with ipsilateral axillary lymph node dissection	Diffuse large B-cell lymphoma	Combination of treatment including surgical excision, chemotherapy, and bone marrow transplantation	[26]
2014	A 75-year-old Malay woman	PBLs	Modified radical mastectomy with level II axillary clearance	ILBCL	Rituximab, cyclophospha-mide, hydroxydaunorubicin, Oncovin (vincristine) and prednisolone (R-CHOP) chemotherapy regimen	[27]
2014	A 47-year-old Japanese female	Invasive ductal carcinoma of the right breast	Right mastectomy with sentinel lymph node biopsy and axillary lymph node dissection	Low grade B-cell lymphoma with plasmacytic differentiation	Spontaneous regression of the MALT lymphoma originally	[8]
2014	A 51-year-old woman	Invasive ductal carcinoma of the breast	Left mastectomy, axillary clearance and right lumpectomy	DLBCL	Epirubicin, vincristine, prednisone and cyclophosphamide (CHOP) chemotherapy with rituximab and planned to follow adjuvant endocrine therapy after chemotherapy	[28]
	A 47-year-old woman	Invasive ductal carcinoma of the breast	Right mastectomy and axillary clearance	DLBCL	6-8 cycles of R-CHOP chemotherapy and planned to follow trastuzumab for one year, and adjuvant endocrine therapy after that
2017	A 65-year-old man	Grade II invasive ductal carcinoma (stage IIA)	Modified radical mastectomy	MCL (stage I, group A)	6 courses of CHOP (A chemotherapy protocol consists of cyclophosphamide 12 g day 1, doxorubicin 80 mg day 1, vindesine 4 mg day 1, and prednisone 90 mg from day 1 to 5) for lymphoma and breast cancer. The patient was also administered endocrine therapy	[29]
2018	A 73-year-old female	Breast cancer	Not mentioned	DLBCL	Not mentioned	[30]
2020	An elderly woman	Grade 2 invasive ductal carcinoma with axillary lymphadenopathy	Mastectomy and axillary node dissection	SLL	Not mentioned	[31]
2019	A woman in her early 60	Invasive ductal carcinoma	Multidisciplina-breast radiotherapy	Diffuse large B-Cell lymphoma	3 coures of R-CHOP and 3 courses of R-CEOP	[32]
2021	A 72-year-old female	Invasive lobular carcinoma of the right breast Stage IIIA (pT2pN3cM0)	Right modified radical mastectomy followed by chemotherapy	Right inguinal lymph node + follicular lymphoma Stage 2 (intermediate risk)	The lymphomas were low grade, which the oncologist closely followed	[33]
	A 60-year-old female	Stage IIB (pT2pN2acM0)	Right mastectomy and right axillary LN dissection, followed by adjuvant chemotherapy and radiotherapy	Abdominal mesenteric lymph node + follicular lymphoma Stage 2 (intermediate risk)
	A 74-year-old female	Multifocal Stage IB (pT1CpN2acM0)	Left mastectomy and complete left axillary dissection followed by chemotherapy and radiotherapy	Follicular neoplasia in situ in two of her left dissected axillary LNStage 1 (low risk)
2021	A 78-year-old male	Breast mucinous carcinoma	Modified radical left mastectomy with lymph node dissection for mucinous carcinoma	Diffuse large B-cell lymphoma	Hormonal therapy with tamoxifen and chemotherapy with the R-CHOP protocol (cyclophosphamide, doxorubi cin, vincristine, and prednisone; given every 21 days for 6 cycles) in combination	[34]
2021	A 72-year-old female	T2N1Mx (stage 2) for the breast cancer	The patient underwent courses of CHOP (cyclophosphamide, doxorubicin, vincris-tine, prednisolone) chemotherapy and was planned for surgery	Chronic lympho cytic leukemia/SLL	The patient underwent courses of CHOP (cyclophosphamide, doxorubicin, vincris- tine, prednisolone) chemotherapy and was planned for surgery	[35]
2021	A 78-year-old woman	Breast invasive ductal carcinoma	Wide local excision of the breast mass with sentinel node biopsy	Abdominal DLBCL	R-CHOP regimen (rituximab 375 mg/m2, vincristine 14 mg/m2, doxorubicin 50 mg/m, cyclophosphamide 750 mg/m2, and prednisolone 100 mg orally). The tumor rapidly relapsed, and the patient received rituximab in combination with gemcitabine and vinorelbine chemotherapy (rituximab 375 mg/m2, gemcitabine 880 mg/m2, vinorelbine 25 mg/m2). Radiotherapy was then administered	[2]
2022	A 35-year-old woman	Invasive ductal carcinoma with no special type grade III (i.e., poorly differentiated) in the breast	Modified radical mastectomy for stage IIIA IDC	NHL	Received R-CHOP chemotherapy for stage I NHL	[1]
2022	A 72-year-old female	Infiltrating ductal carcinoma grade III of the right breast	Resection.	NHL, B cell type, high grade	RHCOP for 6 cycles to overcome lymphoma then received hormonal therapy afterwards	[11]
2024	A 54-year-old post-menopausal female	Breast cancer was staged as Stage IIA	Right breast-conserving surgery with axillary lymph node dissection	DLBCL as Stage IE	3 cycles of R-CHOP protocol. Recommended weekly paclitaxel for 12 cycles and trastuzumab and pertuzumab for 1 year. Endocrine treatment will be started once chemotherapy is completed	[3]

R-CHOP: Rituximab, cyclophosphamide, vincristine, doxorubicin, and prednisolone; DLBCL: Diffuse large B cell lymphoma; RHCOP: Rituximab, cyclophosphamide, epirubicin, vincristin, and prednisone; NHL: Non-Hodgkin Lymphoma; SLL: Small lymphocytic lymphoma; MCL: Mantle cell lymphoma; ILBCL: Intravascular large B-cell lymphoma; MALT: Mucosa-associated lymphoid tissue; PBLs: Primary breast lymphomas; IVLBCL: Intravascular large B-cell lymphoma; CLL: Chronic lymphocytic leukemia.