Table of Contents Author Guidelines Submit a Manuscript
Case Reports in Hematology
Volume 2018, Article ID 2080185, 4 pages
https://doi.org/10.1155/2018/2080185
Case Report

Coexistent Breast Cancer and Essential Thrombocythemia: How We Addressed the Therapeutic Challenges

1Department of Internal Medicine, University of Florida College of Medicine, Jacksonville, FL 32209, USA
2Department of Hematology and Oncology, University of Florida College of Medicine, Jacksonville, FL 32209, USA

Correspondence should be addressed to Karan Seegobin; moc.liamtoh@nibogeesnarak

Received 6 February 2018; Revised 11 May 2018; Accepted 19 July 2018; Published 12 August 2018

Academic Editor: Sergio Storti

Copyright © 2018 Karan Seegobin et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Essential thrombocythemia (ET) occurring with breast cancer is uncommon; the therapeutic approach varies and poses a challenge. A 65-year-old female presented to us after being diagnosed with hormone positive, HER2-negative infiltrating ductal carcinoma. She had a platelet count of 600 thou/cu mm. Her JAK2 mutation was positive. Bone marrow biopsy showed increased megakaryocytes. She was diagnosed with ET in the setting of breast cancer. She underwent breast conservation surgery after which aspirin was resumed. Anticipating thrombocytopenia during chemotherapy and given the absence of data combining hydroxyurea with standard chemotherapy used for breast cancer, we felt it prudent to delay cytoreductive therapy for her ET until after completion of breast cancer treatment. Her average platelet count during chemotherapy was 480 thou/cu mm with the lowest being 377 thou/cu mm. Her platelet count remained at goal between 300 and 350 thou/cu mm after four months of hydroxyurea.

1. Background

Essential thrombocythemia (ET) is a myeloproliferative neoplasm (MPN) [1]. Patients with this condition have an increased risk to develop a second cancer including both haematological [2] and nonhaematological [2, 3] risks. However, breast cancer in the MPN population is not increased in comparison with the general population [4]. Physicians are faced with several therapeutic challenges when ET coexists with another tumour, in particular solid tumours. These should be managed on an individual basis. Physicians should take into consideration the risk of thrombosis, characteristics of the cancer, and the therapeutic approach for the tumour whether surgical, chemotherapy, or both.

2. Case

A 65-year-old female presented with a breast lump, diagnosed to be oestrogen and progesterone receptor positive, HER2 negative, and T1cN1bM0 moderately differentiated infiltrating ductal carcinoma. She had a platelet count of 600 thou/cu mm. There was no history of thrombotic or bleeding episodes.

Further testing showed that JAK2 mutation was positive and t(9;22) mutation was negative. Her bone marrow biopsy showed increased megakaryocytes. Her other lab workup was unremarkable including iron panel and liver function tests. She had no splenomegaly on ultrasound. She was diagnosed with ET in the setting of breast cancer.

Aspirin was commenced but held seven days prior to her breast conservation surgery, restarted postoperatively and continued thereafter. Postoperative thromboprophylaxis with low-molecular weight heparin (LMWH) was continued until the patient was fully ambulatory. Aspirin was restarted on day 7 after the surgery. Anticipating thrombocytopenia during chemotherapy, and given the absence of data combining hydroxyurea with standard chemotherapy used for breast cancer (in this case docetaxel and cyclophosphamide), we felt it prudent to delay cytoreductive therapy for her ET until after completion of breast cancer treatment. Her indication for cytoreductive therapy was >60 years. She was treated with adjuvant docetaxel and cyclophosphamide and continued on aspirin 81 mg for the entire duration of her chemotherapy. She tolerated the 6 cycles of chemotherapy well.

Following the completion of her chemotherapy, she was started on letrozole and radiotherapy with the aim to continue the letrozole for 5 years. Hydroxyurea (500 mg) was also started and titrated to a goal to 400–450 thou/cu mm platelets. Zoledronic acid was started for osteoporosis prevention.

Her average platelet count during chemotherapy was 480 thou/cu mm with the lowest being 377 thou/cu mm (Table 1). Her platelet count remained at goal between 300 and 350 thou/cu mm after four months of hydroxyurea (Table 2). Throughout her treatment, there were no bleeding or thrombotic complications. After one year on letrozole, hydroxyurea, and aspirin, the patient was doing well without complications with platelet counts at goal.

Table 1: Complete blood count (CBC) before, during, and after chemotherapy.
Table 2: Complete blood count after hydroxyurea.

3. Discussion

ET is a myeloproliferative neoplasm and is unique among them because of its natural history, which is compatible with a normal lifespan [1]. It is diagnosed by having platelets more than 450 thou/cu mm in the absence of reactive cause, absence of iron deficiency, presence of JAK2 V617F assay, and haemoglobin less than 14 g/dL in women in the absence of splenomegaly [1, 5]. It is a diagnosis of exclusion, representing clonal or autonomous thrombocytosis not classifiable as any of the following diseases: polycythaemia vera, primary myelofibrosis, chronic myeloid leukaemia, or myelodysplastic syndrome [1]. By this criterion, our patient was diagnosed. Other mutations associated with ET are CALR and MPL which carry prognostic significance [6].

Patients with ET have an increased risk to develop a second cancer, with both haematological and nonhaematological cancers being reported [2].

All patients are managed with aspirin provided there exists no contraindications [7]. It has been shown to reduce the risk of arterial and venous thrombosis in low-risk patients [8]. The indications for cytoreductive therapy include those with a history of thrombosis or age greater than 60 years [7]. The degree of thrombocytosis has not been shown to be a reliable indicator of thrombotic risk [7]. Patients with JAK 2 positivity has been shown to have a greater chance of arterial and venous thrombosis [7]. Hydroxyurea is the only cytoreductive agent proven to reduce thrombotic events in a randomized controlled trial and is the first-line cytoreductive agent [9].

The goal of cytoreductive therapy is to resolve symptoms and normalize the platelet count [7].

Although perioperative thrombotic and bleeding complications appear increased in ET patients, it is not clear whether this can be ameliorated by therapeutic intervention [10]. The management is difficult because there are no definite guidelines available in the literature discussing this issue [11].

Determining the method of cytoreduction is a challenge, as it is important to achieve a balance between such dangerous postoperative complications as vascular thrombosis and excessive haemorrhage [11]. In one report, hydroxyurea was the drug of choice to achieve effective cytoreduction in patients with symptoms of ET—who are intended to undergo cardiac surgery [11]. For patients receiving cytoreductive therapy who are undergoing elective surgery, the blood count is optimized preoperatively, and interruptions in therapy are kept to a minimum [7]. Postoperative thromboprophylaxis is recommended according to usual guidelines for the specific procedure [7]. For patients not receiving cytoreductive treatment, temporary therapy is considered on a case-by-case basis, after assessment of the patient’s thrombotic risk profile, degree of thrombocytosis, and the nature of the surgery [7].

Other malignancies such as tongue cancer, gastric cancer, and colon cancer have been reported in the setting of ET [1214]. ET is likely a coincidental finding in this breast cancer case.

Thrombocytopenia is a well-known side effect of chemotherapy [15, 16]. Considering this, we completed the course of chemotherapy prior to starting hydroxyurea for the patient’s essential thrombocythemia. As expected, our patient’s platelets counts had a downward trend during her course of chemotherapy.

One study conducted on low-risk ET patients showed that antiplatelet therapy reduces the incidence of venous thrombosis in JAK2-mutated patients and the rate of arterial thrombosis in those with cardiovascular risk factors [8]. Aspirin was continued during her chemotherapy treatment, and the patient was monitored closely for bleeding complications. Hydroxyurea was not started during chemotherapy as she did not have a history of thrombotic complications, and we expected her platelet count to drop during the chemotherapy treatment. She did not suffer from thrombotic or bleeding complications during her chemotherapy treatment. A decision to institute cytoreductive therapy should be based on an individual basis.

Survival of ET patients does not substantially differ from that of the general population [17]. On the contrary, the outlook for women with breast cancer varies by the stage of cancer [18]. In general, the survival rates are higher for women with earlier stage cancers [18]. The outlook for each woman is specific to her circumstances [18]. The 5-year relative survival rate for women with stage 0 or stage I breast cancer is close to 100% [18]. For women with stage II breast cancer, the 5-year relative survival rate is about 93% [18]. ET and breast cancer are two malignant disorders with favourable outcomes, and therefore, treatment for one should not preclude treatment for the other.

It is important to recall that letrozole and other aromatase inhibitors can increase the risk of venous thromboembolism (VTE) [19]. Furthermore, in our patient, ET increases her risk for VTE, thus the importance of hydroxyurea to keep platelets at goal cannot be overstated. We have not found any cases of adverse drug interactions between letrozole and hydroxyurea. Furthermore, our patient has been doing well without any adverse effects of such drug combinations. Solid tumours and chemotherapy both increase risk of blood clots [20, 21]. VTE is one of the causes of mortality reported in patients on chemotherapy, though this is less likely in an early stage cancer with low disease burden [21]. In our patient, the risk of VTE from her early stage breast cancer and chemotherapy would likely compound the risk from the underlying myeloproliferative neoplasm, so it is likely essential to counsel these patients on reducing risk by optimizing mobility. Additionally, antithrombotic prophylaxis should be considered during chemotherapy. While it is not routinely recommended in the outpatient setting, it should be considered for high risk patients [22]. The current guidelines indicate that low-molecular weight heparin is the first choice [22]. In our case, we continued postoperative VTE prophylaxis until the patient was fully ambulant; however, every case should be reviewed in a holistic way with consideration given to extending VTE prophylaxis if required. In patients undergoing major abdominal or pelvic surgery with high-risk features, VTE prophylaxis is recommended up to 4 weeks and in other cases, extended up to 6 months [22]. These patients should be periodically reassessed at each follow-up visit to review their risk for VTE [22].

4. Conclusion

(i)Physicians are faced with several therapeutic challenges when ET coexists with solid tumours.(ii)These should be managed on an individual basis.(iii)One should take into consideration the risk of thrombosis and the therapeutic approach for solid tumours in the management of these patients.(iv)Extended VTE prophylaxis during chemotherapy may be needed in select cases.(v)ET and breast cancer both have favourable outcomes, and therefore, treatment for one should not preclude treatment for the other.

Conflicts of Interest

The authors declare that they have no conflicts of interest.

Authors’ Contributions

The idea for reporting this case was that of Lara Zuberi. Further intellectual content and editing was done by all authors. All authors read, edited, and approved the final contents. Karan Seegobin took responsibility for the integrity of the contents.

References

  1. J. L. Spivak and R. T. Silver, “The revised World Health Organization diagnostic criteria for polycythemia vera, essential thrombocytosis, and primary myelofibrosis: an alternativeproposal,” Blood, vol. 112, no. 2, pp. 231–239, 2008. View at Publisher · View at Google Scholar · View at Scopus
  2. H. C. Hasselbalch, “Perspectives on the increased risk of second cancer in patients with essential thrombocythemia, polycythemia vera and myelofibrosis,” European Journal of Haematology, vol. 94, no. 2, pp. 96–98, 2015. View at Publisher · View at Google Scholar · View at Scopus
  3. L. Masarova, M. Cherry, K. J. Newberry et al., “Secondary solid tumors and lymphoma in patients with essential thrombocythemia and polycythemia vera—single center experience,” Leukemia & Lymphoma, vol. 57, no. 1, pp. 237–239, 2016. View at Publisher · View at Google Scholar · View at Scopus
  4. A. R. Landtblom, H. Bower, T. M. Andersson et al., “Second malignancies in patients with myeloproliferative neoplasms: a population-based cohort study of 9379 patients,” Leukemia, 2018. View at Publisher · View at Google Scholar · View at Scopus
  5. D. A. Arber, A. Orazi, R. Hasserjian et al., “The 2016 revision to the World Health Organization classification of myeloid neoplasms and acute leukemia,” Blood, vol. 127, no. 20, pp. 2391–2405, 2016. View at Publisher · View at Google Scholar · View at Scopus
  6. J. Asp, B. Andréasson, U. Hansson et al., “Mutation status of essential thrombocythemia and primary myelofibrosis defines clinical outcome,” Haematologica, vol. 101, no. 4, pp. e129–e132, 2016. View at Publisher · View at Google Scholar · View at Scopus
  7. P. A. Beer, W. N. Erber, P. J. Campbell, and A. R. Green, “How I treat essential thrombocythemia,” Blood, vol. 117, no. 5, pp. 1472–1482, 2011. View at Publisher · View at Google Scholar · View at Scopus
  8. E. Rumi and M. Cazzola, “How I treat essential thrombocythemia,” Blood, vol. 128, no. 20, pp. 2403–2414, 2016. View at Publisher · View at Google Scholar · View at Scopus
  9. S. Cortelazzo, G. Finazzi, M. Ruggeri et al., “Hydroxyurea for patients with essential thrombocythemia and a high risk of thrombosis,” New England Journal of Medicine, vol. 332, no. 17, pp. 1132–1137, 1995. View at Publisher · View at Google Scholar · View at Scopus
  10. M. Ruggeri, F. Rodeghiero, A. Tosetto et al., “Postsurgery outcomes in patients with polycythemia vera and essential thrombocythemia: a retrospective survey,” Blood, vol. 111, no. 2, pp. 666–671, 2008. View at Publisher · View at Google Scholar · View at Scopus
  11. E. Ziadinov, H. Al-Sabti, M. Al-Toubi, and M. S. Siddiqi, “Pretreatment with hydroxyurea of the patient with essential thrombocythemia followed by coronary artery bypass surgery,” Oman Medical Journal, vol. 29, no. 4, pp. 294-295, 2014. View at Publisher · View at Google Scholar · View at Scopus
  12. R. G. Mihăilă, S. Marchian, and R. Mihăilă, “A rare case of thrombocytosis with duble malignant etiology—pathogenetic interrelationships and consequences,” Scholars Journal of Medical Case Reports, vol. 3, no. 8, pp. 684–686, 2015. View at Google Scholar
  13. H. Kondo, Y. Sakai, and T. Takaso, “Coexistence of essential thrombocythemia and gastric cancer,” Rinsho Ketsueki, vol. 34, no. 2, pp. 224–228, 1993. View at Google Scholar
  14. E. Kondo, M. Ueda, T. Yamashita, Y. Nakajima, S. Rin, and M. Fujita, “Therapeutic experience with tongue cancer in a patient who had essential thrombocythemia: a case report,” Japanese Journal of Oral and Maxillofacial Surgery, vol. 58, no. 3, pp. 123–127, 2012. View at Publisher · View at Google Scholar
  15. J. Puente, E. Grande, A. Medina, P. Maroto, N. Lainez, and J. A. Arranz, “Docetaxel in prostate cancer: a familiar face as the new standard in a hormone-sensitive setting,” Therapeutic Advances in Medical Oncology, vol. 9, no. 5, pp. 307–318, 2017. View at Publisher · View at Google Scholar · View at Scopus
  16. A. L Hepburn, S. Narat, and J. C. Mason, “The management of peripheral blood cytopenias in systemic lupus erythematosus,” Rheumatology, vol. 49, no. 12, pp. 2243–2254, 2010. View at Publisher · View at Google Scholar · View at Scopus
  17. F. Cervantes, “Management of essential thrombocythemia,” Hematology, vol. 2011, no. 1, pp. 215–221, 2011. View at Publisher · View at Google Scholar
  18. American Cancer Society, Breast Cancer Facts & Figures 2015-2016, American Cancer Society, Inc., Atlanta, GA, USA, 2015.
  19. J.-M. A. Nabholtz, “Long-term safety of aromatase inhibitors in the treatment of breast cancer,” Therapeutics and Clinical Risk Management, vol. 4, no. 1, pp. 189–204, 2008. View at Publisher · View at Google Scholar
  20. S. Sallah, J. Y. Wan, and N. P. Nguyen, “Venous thrombosis in patients with solid tumors: determination of frequency and characteristics,” Thrombosis and Haemostasis, vol. 87, no. 04, pp. 575–579, 2002. View at Publisher · View at Google Scholar
  21. G. J. Caine, P. S. Stonelake, G. Y. H. Lip, and S. T. Kehoe, “The hypercoagulable state of malignancy: pathogenesis and current debate,” Neoplasia, vol. 4, no. 6, pp. 465–473, 2002. View at Publisher · View at Google Scholar · View at Scopus
  22. G. H. Lyman, K. Bohlke, A. A. Khorana et al., “Venous thromboembolism prophylaxis and treatment in patients with cancer: American Society of Clinical Oncology clinical practice guideline update 2014,” Journal of Clinical Oncology, vol. 33, no. 6, pp. 654–656, 2015. View at Publisher · View at Google Scholar · View at Scopus