Case Report: Bone Marrow Infiltration with Anemia and Thrombocytopenia, Rare Initial Symptoms of Breast Cancer

Abstract

Introduction

Bone metastasis is common in breast cancer, causing pain, myelosuppression, and hypercalcemia. However, bone marrow invasion leading to pancytopenia is exceedingly rare, and its optimal treatment remains a subject of debate. This report presents the first such case from Vietnam, where chemotherapy proved effective.

Case Presentation

A 47-year-old female patient presented to the emergency department with cough, dyspnea, and back pain. Initial laboratory tests revealed WBC 21.83 G/L, neutrophil 10.97 G/L, Hct 27.3%, Hgb 87 g/L, and PLT 22 G/L. Further examination identified a left breast tumor with skin invasion, as well as metastases to the bone, liver, lungs, pleura, cervical lymph nodes, and mediastinal lymph nodes. Bone marrow aspiration confirmed the presence of malignant cell invasion. The patient responded well to chemotherapy with doxorubicin and cyclophosphamide, with platelet counts recovering immediately after the first cycle.

Conclusion

Bone marrow infiltration causing pancytopenia is a rare but serious manifestation of metastatic breast cancer. Management should follow general principles for metastatic breast cancer. Chemotherapy can be considered when rapid disease control is needed or in patients with marrow failure, provided that doses are individualized and treatment is closely monitored. Further data are required to better define optimal therapy in this setting.

Background

Breast cancer is the most common malignancy in women and a leading cause of cancer death worldwide [1]. Metastasis is common in breast cancer and accounts for the majority of disease-related deaths [2]. Although breast cancer can metastasize to all body organs, bone is the most frequent site [2]. Skeletal metastasis typically leads to pathological fractures, spinal cord compression, and hypercalcemia [2]. However, complete bone marrow infiltration resulting in pancytopenia is exceedingly rare [3, 4]. In a review of 22 cases with bone marrow metastasis from breast cancer, only one case developed pancytopenia, while seven others presented with both anemia and thrombocytopenia [5]. According to the limited available case reports, the characteristics of pancytopenia in breast cancer vary across different countries [5–7]. Bone marrow biopsy with immunohistochemistry is considered the gold standard for diagnosing bone marrow infiltration [5, 8]. However, peripheral blood smear or bone marrow cytology has been suggested as a viable alternative in some cases, especially when breast cancer is diagnosed concurrently [5].

Recent advances in systemic therapy have reshaped the management of metastatic breast cancer. For hormone receptor-positive, HER2-negative disease, endocrine therapy combined with CDK 4/6 inhibitors represents the current first-line standard of care [9]. However, in rare cases with visceral crisis or bone marrow failure, upfront chemotherapy may be required to achieve rapid disease control.

In Vietnam, estimated more than 20,000 new cases of breast cancer and over 9,000 related deaths are reported annually [1]. Despite this, information on the manifestations of bone marrow metastasis in breast cancer is scarce. We present a case of breast cancer with thrombocytopenia and anemia caused by diffuse infiltration of the bone marrow by malignant cells.

Case Presentation

A 47-year-old female patient was admitted to the Emergency Department of our hospital due to persistent cough, dyspnea, fatigue, and severe back pain that had lasted for 4 weeks. She had experienced a dry cough for a week, followed by a feeling of tiredness when walking short distances or climbing stairs. The patient also reported pain in the lower part of her back, but no limb numbness or weakness was noted. Although these presenting symptoms worsened daily, she was still able to walk and perform her household chores. She had also self-detected a colorless, painless, well-defined, hard, movable lump on her left breast 4 months prior to hospitalization but did not seek medical care. On the day of admission, the patient suddenly developed dyspnea even at rest, while the heavy dry cough and severe back pain without paralysis remained unchanged.

The patient did not report detecting any lumps in other parts of her body. She had no previous history of any notable disease or family history of breast or other cancers.

Investigations

At the first clinical evaluation, the patient appeared fatigued but was alert and well oriented to person, place, and time. She was afebrile, with a pulse rate of 90 beats per minute, a respiratory rate of 20 breaths per minute, blood pressure of 120/80 mm Hg, and an ECOG Performance Status Scale of 2. Her weight was 44 kg, height was 145 cm, and BMI was 21 kg/m². Lung examination revealed decreased breath sounds at the base of both lungs with some fine crackles over both lungs and no wheezing. Evaluation of her chest revealed a lump located in the central region of the left breast with a peau d’orange appearance and prominent nipple deviation. The lump was approximately 6 cm in diameter, oval-shaped, well defined, hard, painless, and movable. There was no nipple discharge. A palpable, relatively 2-cm, painless, movable lymph node in the left axilla was also noted. She had no paralysis or limb numbness. Cardiac, abdominal, and neurological assessments were normal.

The patient underwent a full-body CT scan, complete blood count, alanine transaminase, aspartate transaminase, serum creatinine, glycemia, serum electrolytes, urine analysis, procalcitonin, and thyroid function tests. The complete blood count revealed severe thrombocytopenia, anemia, and high white blood cells. Her blood test results are summarized in Table 1.

Table 1.

The patient’s complete blood count results

Characteristics	Value	Unit	Reference range
Complete blood count
White blood cells	21.83	G/L	4–10
Neu	10.97	G/L	1.8–7.5
Lym	6.40	G/L	0.8–3.5
Mono	1.95	G/L	0.16–1
Luc	2.01	G/L	0–0.4
RBC	2.92	T/L	3.8–5.5
Hgb	87	g/L	120–175
Hct	27.3	%	35–53
MCV	93.4	fL	78–100
MCH	29.6	pG	26.7–30.7
PLT	22	G/L	150–450
MPV	8.1	fL	7–12

Full-body CT scan revealed multi-organ metastasis including bone, lymph nodes, liver, lungs, and pleura (Fig. 1). Lymph nodes involved included cervical and mediastinal lymph nodes. Bone involvement included multiple vertebrae from the thoracic to lumbar spine, sacrum, both thigh femurs, ribs, and pelvis. The CT scan also revealed both lung consolidation suggesting pneumonitis.

Fig. 1.

Imaging results including bone scan demonstrating multiple bone metastases (a), full-body CT scan demonstrating left breast tumor (arrow) (b), with pleura (c), lungs (d), segment IV of liver (e), mediastinal lymph nodes (arrow) (f), and axillary lymph node (arrow) (g) metastasis.

Core needle biopsy of the lump and bone marrow aspiration were performed. Core needle biopsy showed invasive ductal carcinoma of no special type (grade 3, ER (+8/8), PR (−), HER2 (++)/dual ISH (−), Ki67 (+) 30%). Bone marrow aspiration demonstrated malignant infiltration, whereas a core biopsy with immunohistochemistry was not performed because of severe thrombocytopenia and pneumonitis. Considering the laboratory and imaging tests, a diagnosis of pneumonitis and left breast cancer cT4N3M1 (bones, liver, lungs, pleura, cervical lymph nodes, and mediastinal lymph nodes) with bone marrow invasion resulting in pancytopenia was made.

Differential Diagnosis

Given the patient’s normal BMI and absence of chronic illness, nutritional deficiency was unlikely. Although sepsis-related cytopenia was initially suspected, blood counts failed to normalize after infection control, suggesting that infection alone could not explain the findings [10]. This clinical course supported malignant marrow infiltration as the most plausible etiology.

The multiple lesions in the bones and other organs, coupled with anemia and thrombocytopenia, could suggest multiple myeloma or breast lymphoma with bone marrow infiltration, in addition to breast carcinoma. In multiple myeloma, patients may present with nonspecific symptoms such as nausea, vomiting, malaise, weakness, recurrent infections, or weight loss. Anemia is present in most patients with multiple myeloma at some point during the progression of the disease [11]. Additionally, bone-related problems (e.g., pain from fracture, plasmacytoma, or spinal cord compression), peripheral neuropathy, or hyperviscosity (e.g., dyspnea, transient ischemic attack, retinal hemorrhage, or deep venous thrombosis) can occur. To rule out other possible causes such as multiple myeloma or myelodysplastic syndrome, tests including serum protein electrophoresis, free light chain assay, and marrow cytogenetics or flow cytometry would typically be indicated [11]. However, these could not be performed because of the patient’s critical status and bleeding risk. In the presence of histologically confirmed breast carcinoma and malignant cells in the marrow aspirate, metastatic breast cancer remained the most reasonable diagnosis.

Treatment

She was hospitalized and treated with platelet infusion, broad-spectrum antibiotics, and pain control. With 6 units of RDP, her platelets recovered to 124 G/L. However, 1 week later, when systemic treatment was initiated, the platelet counts steadily dropped to 43 G/L. We decided to administer additional 6 units of RDP, followed by chemotherapy with doxorubicin (60 mg/m² BSA) – cyclophosphamide (600 mg/m² BSA) and zoledronic acid (4 mg/100 mL). Based on experience from previously reported cases worldwide, the dose was reduced by 20% in the first cycle. One week after chemotherapy, her complete blood count improved: WBC 2.94 G/L, neutrophil 1.26 G/L, RBC 3.14 T/L, Hgb 99 g/L, Hct 30.5%, PLT 62 G/L. We continued follow-up with no further immediate treatment. At the beginning of the second cycle, she responded well with no nausea or vomiting, no diarrhea, only hair loss, and her back pain was relieved with a paracetamol/tramadol combination twice daily. The breast tumor also reduced in size. Her complete blood count returned to normal: WBC 10.74 G/L, neutrophil 5.81 G/L, RBC 2.92 T/L, Hgb 93 g/L, Hct 29.3%, PLT 200 G/L. CT scans were obtained every 3 months, and the results showed a partial response. She completed 6 cycles of chemotherapy, after which we switched to endocrine therapy with goserelin 3.6 mg once a month, anastrozole 1 mg every day, and zoledronic acid 4 mg/100 mL every month. During this period, the breast tumor was undetectable, and she felt good, maintained her daily activities, and experienced no more tiredness or uncontrolled back pain.

Outcome and Follow-Up

After 14 months of stable disease, the patient developed jaundice, dyspnea, and increased back pain. The CT scan revealed progression in bone, lungs, and multiple liver metastases. The patient was switched to second-line chemotherapy with paclitaxel 80 mg/m² BSA weekly. After 6 months of treatment with paclitaxel, the disease continued to progress with brain metastasis. The patient died with an overall survival of 21 months. Timeline summary is shown in Figure 2.

Fig. 2.

Timeline of case.

Discussion

Breast cancer commonly spreads to the bones, liver, and lungs. Bone metastasis can lead to complications such as bone fracture, myelosuppression, and hypercalcemia. Although bone metastasis with bone marrow invasion is common in breast cancer, pancytopenia secondary to bone marrow infiltration is extremely rare. Pancytopenia is defined by a decrease in the levels of white blood cells, red blood cells, and platelets. Pancytopenia is often induced by alkylated agents and topoisomerase II inhibitors rather than metastatic disease [6]. There are a few case reports of primary pancytopenia induced by metastatic breast cancer, in which the manifestation of this complication varies worldwide. Despite this, all these reported cases had pancytopenia as the initial presentation of their illness, and breast cancer could be occult [4, 7, 12].

The “seed-and-soil” concept supports preferential bone marrow colonization by circulating tumor cells within a permissive microenvironment rich in vascular and stromal support. This interaction promotes angiogenesis, osteolysis, and local hematopoietic suppression even in the absence of overt radiologic marrow replacement [13]. In solid tumors, such as gastric cancer, up to 30% of patients with marrow metastasis present without extensive bone lesions [14]. These findings suggest that bone marrow failure can arise from stromal and cytokine-mediated suppression rather than massive tumor replacement alone.

This complication can be diagnosed by bone marrow cytology or biopsy with immunohistochemistry to confirm metastasis from breast cancer. Of these diagnostic procedures, bone marrow aspiration and bone marrow biopsy are easy and safe procedures and can be performed in outpatient clinics. Compared with bone marrow biopsy, which may be more likely to be associated with pain and bleeding, bone marrow aspiration is considerably safer and simpler. Although the sensitivity of bone marrow aspiration is significantly lower than that of bone marrow biopsy [8, 15], the specificity of bone marrow aspiration is sufficiently high for the diagnosis of bone marrow invasion. Indeed, it has been documented that bone marrow aspiration had a 47.6% sensitivity, 100% specificity, 100% positive predictive value, and 50% negative predictive value for the diagnosis of advanced breast cancer [15]. After breast cancer was diagnosed in our patient, results of bone marrow cytology combined with the clinical manifestations confirmed bone marrow invasion from breast cancer. Similar to our case, Kopp et al. [5] reported 22 cases with advanced breast cancer, of whom 5 cases had a diagnosis of bone marrow infiltration through performing peripheral blood smear.

The most common histology of bone marrow metastasis from breast cancer is invasive ductal carcinoma, followed by invasive lobular carcinoma. Hormone receptors are detected in 50–80% of cases. In addition, anemia and thrombocytopenia are the most common manifestations of bone marrow infiltration [5]. We similarly found that our patient had invasive ductal carcinoma and hormone receptor positivity.

To date, there are no guidelines for the treatment of metastatic breast cancer with pancytopenia due to a lack of data regarding effective and safe treatment for this complication. Hence, the treatment of patients with complete bone marrow failure requires a cautious approach. Reports have shown that bone marrow metastasis can be treated with low-dose capecitabine, doxorubicin, trastuzumab monotherapy, or hormonal therapy [5, 16–18]. However, the treatment of bone marrow metastasis in patients with hormone receptor-positive breast cancer may involve chemotherapy instead of endocrine therapy. In a case reported by Jindal et al. [7], a patient with ER-positive breast cancer, bone metastasis with pancytopenia was treated with letrozole and palbociclib. Soon after starting the therapy, the patient developed immune thrombocytopenia and autoimmune hemolytic anemia. The results of her direct antiglobulin test were positive for immunoglobulin G. Therefore, she received steroid therapy and her therapy with CDK 4/6 inhibitor plus aromatase inhibitor was discontinued. The patient started chemotherapy with capecitabine. She had a good response to this therapy with counts slowly returning to the reference range over the next 4 to 6 months.

In another case, Pahouja et al. [4] showed that a patient with symptomatic total bone marrow failure survived for 44 months with continuous low-dose doxorubicin followed by hormone treatment. Kopp et al. [5] reported that 22 cases with symptomatic bone marrow metastasis were treated with a cytotoxic regimen. The best response (5 in these 22 cases) was from multiple chemotherapy with docetaxel and anthracycline. Recently, Akagi et al. [16] reported a similar case, where the patient was treated with doxorubicin and cyclophosphamide, with the dose reduced by 20% in the first cycle due to anemia and thrombocytopenia. The complete blood count steadily recovered after the first cycle of treatment. In this case, the patient was treated with 8 cycles of doxorubicin-cyclophosphamide and docetaxel, and then was switched to exemestane.

In this case, the decision to initiate doxorubicin-cyclophosphamide at a 20% reduced dose was made to balance efficacy and safety. The rapid hematologic recovery after the first cycle confirmed that chemotherapy could be continued safely. This experience highlights the importance of individualized dose modification and close monitoring when managing metastatic breast cancer with bone marrow involvement.

It has been documented that pancytopenia induced by bone marrow infiltration in patients with metastatic breast cancer has a poor prognosis. Kopp et al. [5] found that a partial response and stable disease were the best responses after chemotherapy treatment in bone marrow infiltration by metastatic breast cancer in 22 patients. There was no complete response, and the median overall survival time was 19 months. Pahouja et al. [4] found that the no-progression interval was 32 months, and overall survival was 44 months. Our patient had an overall survival interval of 21 months.

On the contrary, one report of Garufi et al. [9] also described about the pancytopenia in patient with breast cancer, the treatment was started with hormonal therapy and CDK 4/6 inhibitor, the total blood count returned to normal after 4 months of treatment, and complete remission was reached after 26 months of treatment. But the difference we noticed in this report is this patient just has mild symptoms and grade 1 pancytopenia, so CDK 4/6 inhibitor and aromatase inhibitor worked successfully.

Conclusions

Bone marrow infiltration causing pancytopenia is a rare but serious manifestation of metastatic breast cancer. Because cytopenia may result from multiple concurrent mechanisms, the relationship between marrow involvement and hematologic failure should be interpreted with caution. Management should follow general principles for metastatic breast cancer. Chemotherapy can be considered when rapid disease control is needed or in patients with marrow failure, provided that doses are individualized and treatment is closely monitored. Further data are required to better define optimal therapy in this setting. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000549915).

Learning Points/Take-Home Messages

• Breast cancer can lead to bone marrow infiltration and subsequent pancytopenia, a serious complication requiring prompt diagnosis and treatment.

• Bone marrow cytology and biopsy can be used to diagnose bone marrow invasion by metastatic breast cancer.

• Chemotherapy dosing and regimen may need to be tailored to individual patients, and a cautious approach is warranted in managing patients with complete marrow failure.

Statement of Ethics

This retrospective review of patient data did not require ethical approval in accordance with national guidelines. The written informed consent was obtained from the patient’s next-of-kin for publication of the details of this medical case and any accompanying images.

“I am the patient’s sister and consent to the publication of this case report, including any identifying information, in “Case Report: Bone Marrow Infiltration with Anemia and Thrombocytopenia, Rare Initial Symptoms of Breast Cancer”. I understand that this information will be published online and may be seen by the general public. I am aware that anonymity cannot be guaranteed.”

Conflict of Interest Statement

The authors have no conflicts of interest to declare.

Funding Sources

This study was not supported by any sponsor or funder.

Author Contributions

T.Q.L. constructed an idea for manuscript. K.D.H. took responsibility in patient follow-up and data management. N.P.L., T.V.T., and T.T.D.N. took responsibility in literature review. M.T.N.T. took responsibility in the construction of the whole body of the manuscript, and organized and supervised the course of the article. All authors contributed to the final manuscript.

Funding Statement

This study was not supported by any sponsor or funder.

Data Availability Statement

The data analyzed during this study are included in this published article (and its supplementary information files). Further inquiries can be directed to the corresponding author.