Incidental [⁶⁸Ga]Ga-DOTATATE uptake in bone metastases of breast carcinoma in a patient with a secondary carcinoid tumor

Abstract

Background

Lobular breast cancer often shows only low [¹⁸F]FDG uptake, limiting the sensitivity to detect metastases. Alternative tracers, targeting tumor activated fibroblasts or estrogen receptors, can offer higher accuracy. Also, Somatostatin Receptor 2 (SSTR2) is significantly expressed in some breast cancers, particularly in estrogen receptor rich tumors. Typical pulmonary carcinoids also have low [¹⁸F]FDG accumulation, but approximately 63% of well-differentiated lesions express SSTR2.

Case presentation

We report the case of a 66-year-old female patient with lobular breast cancer and a coincidentally discovered typical carcinoid of the lung. On subsequent [⁶⁸Ga]Ga-DOTATATE PET/CT to stage the carcinoid tumor, two SSTR2 positive focal lesions in the bones were present, without [¹⁸F]FDG uptake but with mild sclerosis, atypical for metastasis of carcinoids. Biopsy confirmed osseous breast cancer metastases.

Conclusion

SSTR2 expression in normal breast tissue and breast carcinoma has been described previously. However, the case underscores the importance of awareness of atypical presentations of cancer within a multi-tracer approach, whereby receptor profile and morphology must be carefully integrated.

Supplementary Information

The online version contains supplementary material available at 10.1186/s13550-026-01462-4.

Background

Lobular breast cancer is known to demonstrate low [¹⁸F]-FDG uptake in some cases, limiting the sensitivity for PET/CT in the detection of metastases [1]. Therefore, occult lesions on [¹⁸F]-FDG PET/CT have to be searched with contrast enhanced CT or MRI [2, 3]. Alternative PET tracers, including the fibroblast-activation protein inhibitors (FAPI) or targeting the estrogen receptors (ER) are under investigation to improve accuracy in staging lobular breast cancer [4, 5]. However, widespread availability is still limited for both alternatives. First preclinical tests suggested that agonistic somatostatin receptor 2 (SSTR2) ligands (such as [⁶⁸Ga]Ga-DOTATATE, [⁶⁸Ga]Ga-DOTATOC or [¹¹¹In]In-DOTA-JR11), might provide higher sensitivity and specificity, in particular, in ER-rich tumors [6, 7]. Early clinical investigations suggested a potential role of [^99mTc]Tc-Octreotide imaging [8] and subsequent clinical investigations confirmed the potential use of [⁶⁸Ga]Ga-DOTATATE to image ER-rich breast cancer [9, 10]. One study even suggested that [²²⁵Ac]Ac-DOTATATE might be a promising therapeutic option for some patients with SSTR2 positive breast cancer [10].

[⁶⁸Ga]Ga-DOTATATE is typically used in imaging neuroendocrine tumors (NET), arising for the gastrointestinal tract or the lungs since these lesions have low [¹⁸F]-FDG-accumulation [11, 12]. Well-differentiated pulmonary carcinoids have up to 63% high SSTR2 expression on [⁶⁸Ga]Ga-DOTATATE PET/CT¹¹.Therefore, the low [¹⁸F]-FDG-uptake in a pulmonary lesion could be compatible with a carcinoid as well as metastasis from a lobular breast cancer and biopsy is needed. If then [⁶⁸Ga]Ga-DOTATATE PET/CT is done to stage the pulmonary carcinoid, a positive lesion could still represent a metastasis from lobular breast cancer. This is important to know, since pulmonary carcinoids are often incidental findings in patients undergoing chest CT, with over 40% of the lesions incidentally discovered [13] and around 43% then staged with SSTR2 targeting imaging [14].

Case presentation

We present the case of a 66-year-old woman with a history of lobular carcinoma of the right breast (ER 100%, HER2-negative, Ki-67 20%) who underwent breast-conserving surgery in March 2025. CT imaging performed for radiotherapy planning revealed a pulmonary nodule with 17 mm in the left lower lobe. To rule out pulmonary metastasis a [¹⁸F]-FDG PET/CT was performed and showed only minimal metabolic activity in this lesion (Fig. 1). Based on the low [¹⁸F]FDG accumulation in a pulmonary nodule, a metastasis from a lobular breast cancer could not be ruled out, however primary pulmonary tumor was possible as well. Therefore, a bronchoscopy with biopsy was recommended and showed pulmonary carcinoid, without evidence for breast cancer metastasis (NET, G1, Ki-67 5%, synaptophysin and chromogranin positive, ER-negative), consistent with the known low [¹⁸F]-FDG avidity of typical carcinoids. Subsequent [⁶⁸Ga]Ga-DOTATATE PET/CT for staging of the carcinoid lesion demonstrated intense SSTR2 uptake in two bone lesions in the left iliac bone and right humeral head, whereas the pulmonary nodule showed only faint uptake. The bone lesions showed mild sclerosis on CT. Given that strong SSTR2 positive bone metastasis arising from a SSTR2 negative primary tumor would be unusual, as well as primary sclerotic bone lesions are not typical for a pulmonary carcinoid, a biopsy of the iliac lesion was recommended. The iliac lesion was confirmed to be metastatic lobular breast cancer.

Fig. 1.

66-year-old woman after resection of a lobular carcinoma of the right breast. [¹⁸F]FDG PET/CT (A1) - axial fused image, the paracardial lesion (yellow arrow) has low metabolic activity. Biopsy showed a typical carcinoid (NET G1, Ki-67 5%, Estrogen receptor-negative). For staging of the pulmonary carcinoid, a [⁶⁸Ga]Ga-DOTATATE PET/CT was performed and the axial fused image (A2) showed only faint somatostatin receptor 2 (SSTR2) expression (red arrow). Whole-body maximum intensity projection of [¹⁸F]FDG PET/CT (B1) shows no increased uptake in the bones. However, on [⁶⁸Ga]Ga-DOTATATE PET/CT (B2) two bone lesions with intense [⁶⁸Ga]Ga-DOTATATE uptake were detected (red arrows). On axial fused [¹⁸F]FDG PET/CT (C1/D1) sclerotic changes, without [¹⁸F]FDG uptake were seen (yellow arrow), where fused [⁶⁸Ga]Ga-DOTATATE PET/CT showed strong SSTR2 expression (SUVmax 10.2) (red arrow) in the right humeral head lesion (C2) as well as in the left iliac lesion (D2). The iliac bone lesion was biopsied and a SSTR2 positive bone metastases of the lobular breast cancer confirmed

Based on these findings, the patient started on endocrine therapy with letrozole and the CDK4/6 inhibitor abemaciclib, with partial response on subsequent [⁶⁸Ga]Ga-DOTATATE of both bone lesions. The pulmonary carcinoid remains under surveillance.

Conclusion

This case illustrates the crucial role of a molecular multi-tracer imaging approach in complex oncological scenarios. SSTR expression in normal breast tissue and breast carcinoma has been described in the literature. Although SSTR2 expression is often interpreted as indicative of neuroendocrine tumors, recognizing that SSTR2 expression in bone metastases from breast cancer can be an incidental yet highly useful finding helps guide patient management. Ultimately, knowledge about morphological patterns and histopathological workup in unclear cases remains essential to guide therapy and avoid misclassification of lesions.

Supplementary Information

Below is the link to the electronic supplementary material.

Abbreviations

ER

Estrogen receptor

FAPI

Fibroblast-activation protein inhibitors

SSTR2

Somatostatin receptor 2

NET

Neuroendocrine tumor

Author contributions

Data collection and literature research (JK, SGP, RP), conceptual input (AS, CP, TN, CL and IAB), pathology analysis (GS), Manuscript draft writing (JK, SGP, IAB, CL). Approval of manuscript (JK, SGP, RP, AWS, TN, GS, CL, IAB).

Funding

There was no specific funding for this work.

Data availability

Data are available upon reasonable request to the corresponding author.

Declarations

Ethics approval and consent to participate

The patient gave written consent for the publication of this case report. Ethics approval is not applicable.

Consent for publication

The patient gave written consent for the publication of this case report.

Competing interests

All authors declare no conflict of interest or competing interests for this work.