Case Report: Liver Metastasis from Ductal Carcinoma In Situ of the Breast

Introduction

Breast cancer is the most common malignant tumor in women worldwide with high morbidity and mortality.¹ Ductal carcinoma in situ (DCIS) is defined as a malignant proliferation of ductal epithelial cells confined within the basement membrane, belonging to non-invasive breast cancer (stage 0).² Breast cancer statistics show that DCIS accounts for a considerable proportion of newly diagnosed breast cancer cases,³ and its biological behavior and metastatic potential have been a research focus in recent years.⁴

Distant metastasis of DCIS is an extremely rare event with an incidence of less than 0.5%, and liver metastasis is even rarer.⁵ The balance between overtreatment and undertreatment of DCIS has always been a clinical focus, and the rare occurrence of distant metastasis further complicates this balance.⁶ Although DCIS is traditionally considered to have no metastatic potential, increasing case reports have confirmed that distant metastasis, especially liver metastasis, can occur in a few high-risk DCIS patients.^7,8 The rarity of DCIS liver metastasis leads to insufficient clinical awareness, unclear risk stratification, and lack of standardized treatment strategies.⁹

DCIS accounts for approximately 30% of newly diagnosed breast cancer cases.¹⁰ Most DCIS patients have a favorable prognosis after surgical treatment, but a small number of high-risk patients may develop early distant metastasis, which is related to missed microinvasion, high nuclear grade, large tumor size, and HER2 positivity.^11,12 The epidemiology of liver metastases in breast cancer has been studied, but data on DCIS-related liver metastasis are extremely limited.¹³ Due to the extreme rarity of DCIS liver metastasis, there is still a lack of systematic literature summary and unified treatment norms.¹⁴

Dietary interventions and metabolic regulation may have potential implications for liver metastatic breast cancer, but their role in DCIS-related liver metastasis remains unclear.¹⁵ This paper reports a rare case of liver metastasis after surgery for high-grade, HER2-positive, large-volume DCIS, emphasizes the metastatic potential and rarity of DCIS, summarizes the high-risk factors and evidence levels of DCIS distant metastasis, and analyzes the efficacy of TCbHP regimen, aiming to improve clinicians’ awareness and diagnosis-treatment level of this rare event.¹⁶

Case Presentation

General Information

A 35-year-old premenopausal married female was admitted due to “left breast mass for 2 months”. Height 160 cm, weight 65 kg, BMI 25.4 kg/m². No smoking, drinking, toxic exposure, or family history of malignant tumors. Physical examination: a 4 cm × 4 cm mass in the upper inner quadrant of the left breast, medium hard texture, clear boundary, no tenderness, good mobility, no adhesion to skin. Radiological examination of the breast has certain guiding significance for the diagnosis of DCIS, and this patient’s imaging features were consistent with high-risk DCIS manifestations.¹⁰

Diagnosis and Treatment Process

Initial diagnosis and surgery: On September 24, 2021, left breast tumor segmentectomy was performed; postoperative pathology suggested DCIS. Interobserver variability in DCIS diagnosis should be noted, and multiple sections were examined to ensure diagnostic accuracy.¹¹ On October 12, 2021, “left simple mastectomy + left sentinel lymph node biopsy” was performed.

Pathological results: High-grade DCIS (5.0 cm × 3.5 cm); IHC: ER(−), PR(−), HER-2(2+), Ki-67(30%+); FISH positive; pathological stage TisN0M0. Some DCIS cases may present with DCIS-like invasive ductal carcinoma, but this case was confirmed as pure DCIS without invasive components.¹² The pathological features of DCIS, including nuclear grade and tumor size, are important prognostic factors.¹⁴ No adjuvant therapy was given postoperatively.

Metastasis diagnosis: In January 2022, follow-up abdominal ultrasound found multiple hepatic space-occupying lesions; enhanced MRI suggested multiple metastatic tumors. Liver puncture on March 2, 2022, confirmed adenocarcinoma, consistent with breast cancer origin (IHC: ER(−), PR(−), C-erbB2(2+), Ki-67(40%+), FISH positive). Liver metastasis occurred about 5 months after surgery. Similar cases of distant metastasis after mastectomy for DCIS have been reported, but liver metastasis is still relatively rare.¹⁷

Treatment plan: Implantable venous port was placed, and TCbHP regimen was started on March 21, 2022 (docetaxel 130 mg + carboplatin 690 mg + trastuzumab 390 mg [initial dose 520 mg] + pertuzumab 420 mg [initial dose 840 mg], q3w). After 10 cycles, maintenance therapy was given: trastuzumab 390 mg + pertuzumab 420 mg + capecitabine 1.5 g bid. Integrative studies on key genes driving DCIS progression have provided a theoretical basis for targeted therapy.¹⁸

Efficacy: After 10 cycles of TCbHP, liver metastases achieved complete remission (CR); maintenance therapy showed stable disease (SD) without recurrence. The evolution of DCIS treatment has emphasized the importance of stratified management, and targeted therapy for high-risk DCIS has gradually become a research focus.¹⁹

Auxiliary Examinations

Tumor markers: Abnormal elevation during metastasis, which returned to normal after treatment (Table 1).

Table 1 Tumor Markers From September 22, 2021 to October 5, 2022

Imaging: Breast ultrasound (BI-RADS 4A) and mammography (BI-RADS 4B) suggested malignant lesions; abdominal ultrasound and enhanced MRI showed multiple liver metastases (Figures 1–13). Radiological examination plays an important role in the follow-up and metastasis detection of DCIS.¹⁰

Figure 1 Ultrasonography revealed a patchy hypoechoic area in the left breast, assessed as BI-RADS category 4A, two dotted lines reveal the maximum cross-sectional area of the tumor.

Figure 2 Mammography revealed regional, diffuse, fine pleomorphic calcifications in the medial left breast, for which malignancy could not be excluded, warranting further investigation (BI-RADS 4B). The right breast showed focal asymmetry in the lower breast, recommended for short-term follow-up (BI-RADS 3).

Figure 3 Abdominal Ultrasound Image (20 January 2022). The dotted line is used to measure the maximum cross-sectional distance of the lesion, and (+) indicates the starting and ending points of the measurement.

Figure 4 Abdominal Ultrasound Image (26 February 2022). The dotted line is used to measure the maximum cross-sectional distance of the lesion, and (+) indicates the starting and ending points of the measurement.

Figure 5 Abdominal Ultrasound Image (1 June 2022).

Figure 6 Contrast-enhanced abdominal magnetic resonance image (22 February 2022).

Figure 7 Contrast-enhanced abdominal magnetic resonance image (20 April 2022).

Figure 8 Contrast-enhanced abdominal magnetic resonance image (1 June 2022).

Figure 9 Contrast-enhanced abdominal magnetic resonance image (14 July 2022).

Figure 10 Contrast-enhanced abdominal magnetic resonance image (6 August 2022).

Figure 11 Contrast-enhanced abdominal magnetic resonance image (7 October 2022).

Figure 12 Contrast-enhanced abdominal magnetic resonance image (3 December 2022).

Figure 13 Contrast-enhanced abdominal magnetic resonance image (7 February 2023).

Pathology: Breast high-grade DCIS and liver metastatic adenocarcinoma were confirmed by pathology and IHC (Figures 14–17). DCIS with microinvasion is often considered a borderline between in situ and invasive disease, but this case had no definite microinvasion.⁵

Figure 14 Pathological image of breast mass.

Figure 15 Fluorescence in situ hybridization of breast mass.

Figure 16 Pathological image of liver metastasis tumor biopsy.

Figure 17 Fluorescence in situ hybridization of liver metastasis tumor biopsy.

Timeline: See Figure 18.

Figure 18 The timeline of this case report.

Discussion

Rarity and Mechanism of DCIS Distant Metastasis

DCIS distant metastasis is extremely rare with an incidence lower than 0.5%.⁵ According to systematic literature review, fewer than 100 cases of DCIS distant metastasis have been reported worldwide, and only 15–20% of them are liver metastasis.¹⁷ Rare presentations of metastatic breast cancer from stage 0/1 disease, including DCIS, have been reported, but liver metastasis remains uncommon.¹⁶ The core pathological mechanism is mostly related to missed microinvasion in the initial pathological diagnosis, which means tumor cells break through the basement membrane with foci ≤1 mm and cannot be identified by routine sampling.^5,14

High nuclear grade, large tumor diameter (>3 cm), HER2 positivity, high Ki-67, and young age are the main high-risk factors for DCIS metastasis.¹⁹ These factors promote tumor proliferation, angiogenesis, and invasive ability, which increase the risk of early distant metastasis even if the pathological diagnosis is pure DCIS.²⁰ The oncogene HER2 plays a key role in the metastasis of breast cancer, including DCIS, by activating related signaling pathways.²⁰ This case fully conforms to the above high-risk characteristics, which also explains the reason for early liver metastasis after surgery.

High-Risk Factors for DCIS Distant Metastasis and Evidence Levels

Combined with the latest literature and guidelines (NCCN 3.2024, CSCO 2025),^21,22 the recognized high-risk factors for DCIS distant metastasis and evidence levels are summarized as follows:

A. High nuclear grade: Evidence level IIA; high-grade DCIS has stronger proliferation and invasion potential.⁵

B. Tumor diameter >3 cm: Evidence level IIA; large-volume DCIS is more likely to have focal microinvasion.^10,19

C. HER2 positivity: Evidence level IB; HER2 overexpression activates PI3K/AKT and MAPK pathways to enhance metastasis.²⁰

D. High Ki-67 expression (≥20%): Evidence level IIB; reflects strong tumor proliferation activity.¹⁹

E. Microinvasion: Evidence level IA; microinvasion foci are the direct source of distant metastasis.⁵

F. Young age (<40 years old): Evidence level IIB; young patients have more active tumor biology.¹⁹

This case matches all the above high-risk factors: high grade, tumor size 5.0 cm (>3 cm), HER2 positive, Ki-67 30% (≥20%), young age (35 years old), which is consistent with the high-risk characteristics of DCIS distant metastasis.

Treatment Options for DCIS Liver Metastasis and Efficacy

DCIS liver metastasis is rare, and its treatment refers to the norms of invasive breast cancer liver metastasis:^7,8

Systemic therapy: The first choice for multiple metastases; HER2-positive patients prefer dual-targeted therapy combined with chemotherapy.^21,22

Local treatment: Surgical resection or ablation for isolated oligometastases.^7,8

Maintenance therapy: Targeted therapy combined with chemotherapy to prolong progression-free survival.^21,22

Efficacy of common regimens:

HER2-positive metastatic breast cancer: Trastuzumab + pertuzumab + chemotherapy can achieve an objective remission rate (ORR) of 80%–90%, and median progression-free survival (PFS) of 18.7 months.²¹

TCbHP regimen (docetaxel + carboplatin + trastuzumab + pertuzumab): It is a first-line regimen for HER2-positive metastatic breast cancer with strong efficacy and manageable safety.²¹

Diagnostic and Therapeutic Highlights of This Case

A. Rare event confirmation: This is a typical rare case of liver metastasis from high-risk DCIS, which is rarely reported in domestic and foreign literature.^16,17

B. High-risk feature matching: Fully consistent with the recognized high-risk factors of DCIS distant metastasis, providing clinical evidence for risk stratification.^21,22

C. Remarkable efficacy of TCbHP regimen: 10 cycles of treatment achieved complete remission of liver metastases, confirming that dual anti-HER2 targeted combined chemotherapy is effective for HER2-positive DCIS liver metastasis.^20,21

D. Guideline-based treatment: Treatment intensity refers to invasive breast cancer, verifying the rationality of stratified management of high-risk DCIS.^21,22

Limitations

This study has several limitations. First, this is a single-case report from a single center, and the conclusion needs to be verified by more cases. Second, the initial pathological section did not find definite microinvasion foci, so the direct cause of metastasis cannot be fully confirmed. Third, the follow-up time is relatively short, and long-term survival data need to be further collected.

Clinical Implications

A. Pathological diagnosis: For large-volume, high-grade, HER2-positive DCIS, full-sample pathological examination should be performed to exclude microinvasion.⁵

B. Risk stratification: High-risk DCIS patients should receive close follow-up (abdominal imaging every 3–6 months) to detect metastasis early.¹⁰

C. Adjuvant therapy: For HER2-positive, large-volume, high-grade DCIS, adjuvant targeted therapy can be considered to reduce metastasis risk.^19,21

D. Metastasis treatment: Once metastasis occurs, systemic therapy based on anti-HER2 dual-targeted therapy should be initiated immediately to improve prognosis.^7,8

Conclusions

DCIS distant metastasis is extremely rare, and liver metastasis is an uncommon manifestation of metastatic DCIS. High-grade, tumor >3 cm, HER2 positivity, high Ki-67, and young age are independent high-risk factors with moderate-to-high evidence levels. TCbHP regimen has significant efficacy in the treatment of HER2-positive DCIS liver metastasis and can achieve complete remission. High-risk DCIS should adopt stratified management, and treatment intensity should refer to invasive breast cancer to improve prognosis.