The Breast 24 (2015) 283e284
Contents lists available at ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Letters to the Editor
Other factors related to the completion of treatment after breast cancer Dear Editor, We read the article “Factors related to incomplete treatment of breast cancer in Kumasi, Ghana.” The authors found that religion type, believing in traditional treatments, and lack of awareness of national health insurance coverage were the factors for ceasing the treatment [1]. A randomized controlled study assessed the factors related to coping strategies for women completing breast cancer treatment, which were not evaluated in this article. They reported that positive problem solving, escape/avoidance, and seeking social support were the significant factors [2]. Moreover, the authors commented that Islamic women were focused on fatalism, and they did not complete the treatment because many physicians were male. If these statements were true, then the Islamic women would not have chosen surgical treatment or would not have been operated on by male surgeons, relevant issues that were not reported in the study.
Breast 2014;23(6):821e8. http://dx.doi.org/10.1016/j.breast.2014.08.014. pii: S0960e9776(14)00163-5[Epub ahead of print]. [2] Rosberger Z, Edgar L, Collet JP, Fournier MA. Patterns of coping in women completing treatment for breast cancer: a randomized controlled trial of nucare, a brief psychoeducational workshop. J Psychosoc Oncol 2002;20(3):19e37.
Ahmet Korkut Belli* Department of General Surgery, Mugla Sitki Kocman Medical School, Mugla, Turkey Funda Elibol Department of Radiology, Mugla Sitki Kocman Medical School, Mugla, Turkey E-mail address: [email protected]. Onder Ozcan Department of General Surgery, Mugla Sitki Kocman Medical School, Mugla, Turkey E-mail address: [email protected]. *
Conflict of interest statement There is no conflict of interest. Ethical approval
Corresponding author. Mugla Sitki Kocman University Medical School, Department of General Surgery, Mugla 48000, Turkey. E-mail address: [email protected] (A.K. Belli). 12 January 2015 Available online 26 February 2015
Ethical approval was not required. References [1] Obrist M, Osei-Bonsu E, Awuah B, Watanabe-Galloway S, Merajver SD, Schmid K, et al. Factors related to incomplete treatment of breast cancer in Kumasi, Ghana.
http://dx.doi.org/10.1016/j.breast.2015.02.003 © 2015 Elsevier Ltd. All rights reserved.
Prognosis of women with early breast cancer and PIK3CA mutations Sabine et al. (September 20 issue of Journal of Clinical Oncology) state that “PIK3CA mutations do not seem to affect residual risk following treatment with endocrine therapy” [1]. The Authors argue that there is a complex relationship between risk of recurrence and PIK3CA mutations since PIK3CA mutations are associated with multiple low-risk prognostic features in early breast cancer. Prognostic significance of PIK3CA activation has been widely analyzed in the scientific literature and PIK3CA somatic mutations
were never linked to poor prognosis [2]. This means the data reported by Sabine et al. are not striking as stated by the Authors. If we look instead at abnormal activation of the PI3K/Akt/mTOR pathway in germ cells we immediately realize it drives hamartoma growth. Of note hamartoma syndromes are manifested by benign tumors in multiple organs, nevertheless affected individuals have an increased risk of developing certain malignant cancers, and they usually also have a decreased life span compared to the
284
Letters to the Editor / The Breast 24 (2015) 283e284
general population [3]. Whether the role of PIK3CA mutations rises in a further phase by selective pressure (which could be also dependent on oncologic treatment) also in the somatic mutations setting is yet to be explored. For this purpose it would be useful to compare mutation positive and mutation negative patients regarding overall survival data in the Authors' database. In addition, the PI3K pathway is complex and it is now known that not only the mutations of the kinase, but also the loss of negative regulators such as PTEN and the expression of growth factors matter in the regulation of this route [4]. A limit of the analysis of a single marker is therefore represented by the fact that the control (i.e. the population without the marker of interest) has other factors involved in the activation of the pathway. To overcome this problem, it might be useful to deepen the analysis of the pathway with alternative techniques as stated by the Authors. Alternatively, a greater characterization of the population affected by the mutations can be attempted. The logistic regression analysis of prognostic factors shown by Sabine et al. is of great help, but it would be more interesting and with several direct clinical implication a tentative analysis of the distribution of mutations and the corresponding prognosis in pre-defined groups of patients, in particular in patients with variable expression of hormone receptors. The Authors comment that the kinase mutations are more frequently associated with the expression of PgR. Perhaps the data should be read in reverse, meaning that patients with mutations in the helical domain have more luminal B phenotype than the remaining patients. A much more important issue for patients with breast cancer is whether a relationship exists between PIK3CA mutations and benefit with a specific type of therapy. Yet, PIK3CA mutations have been reported to confer resistance to endocrine therapy [5]. Counterintuitively, the data by Sabine et al. go in the opposite direction. In order to interpret this data, we would like to point out that recent studies have shown that loss of PIK3CA mutations after neoadjuvant chemotherapy selects patients with better prognosis [6]. If patients treated within the TEAM study have differential response to chemotherapy based on the presence of mutations in PIK3CA this has to be taken into account, because the lack of difference in outcome between wild type and mutated PIK3CA patients
http://dx.doi.org/10.1016/j.breast.2015.02.028 © 2015 Elsevier Ltd. All rights reserved.
compared to hormonal therapy might be offset by an increased sensitivity to chemotherapy. We hope that current research on PI3K signaling will shed some additional light on the aforementioned topics.
References [1] Sabine VS, Crozier C, Brookes CL, Drake C, Piper T, van de Velde CJH, et al. Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study. J Clin Oncol 2014;32:2951e9. [2] Pang B, Cheng S, Sun SP, An C, Liu ZY, Feng X, et al. Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis. Sci Rep 2014;4:6255. [3] Orloff MS, He X, Peterson C, Chen F, Chen JL, Mester JL, et al. Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet 2013;92:76e80. [4] Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489e501. [5] Crowder RJ, Phommaly C, Tao Y, Hoog J, Luo J, Perou CM, et al. PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer. Cancer Res 2009;69: 3955e62. [6] Jiang YZ, Yu KD, Bao J, Peng WT, Shao ZM. Favorable prognostic impact in loss of TP53 and PIK3CA mutations after neoadjuvant chemotherapy in breast Cancer. Cancer Res 2014;74:3399e407.
Serena Di Cosimo*, Giulia Valeria Bianchi, Giacomo Bregni, Filippo de Braud Department of Oncology, Istituto Nazionale dei Tumori, Milano, Italy *
Corresponding author. Department of Oncology, Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy. Tel.: þ39 02 2390 3066; fax: þ39 02 2390 2049. E-mail address: [email protected] (S. Di Cosimo). 24 November 2014 Available online 12 March 2015
Contents lists available at ScienceDirect
The Breast journal homepage: www.elsevier.com/brst
Letters to the Editor
Other factors related to the completion of treatment after breast cancer Dear Editor, We read the article “Factors related to incomplete treatment of breast cancer in Kumasi, Ghana.” The authors found that religion type, believing in traditional treatments, and lack of awareness of national health insurance coverage were the factors for ceasing the treatment [1]. A randomized controlled study assessed the factors related to coping strategies for women completing breast cancer treatment, which were not evaluated in this article. They reported that positive problem solving, escape/avoidance, and seeking social support were the significant factors [2]. Moreover, the authors commented that Islamic women were focused on fatalism, and they did not complete the treatment because many physicians were male. If these statements were true, then the Islamic women would not have chosen surgical treatment or would not have been operated on by male surgeons, relevant issues that were not reported in the study.
Breast 2014;23(6):821e8. http://dx.doi.org/10.1016/j.breast.2014.08.014. pii: S0960e9776(14)00163-5[Epub ahead of print]. [2] Rosberger Z, Edgar L, Collet JP, Fournier MA. Patterns of coping in women completing treatment for breast cancer: a randomized controlled trial of nucare, a brief psychoeducational workshop. J Psychosoc Oncol 2002;20(3):19e37.
Ahmet Korkut Belli* Department of General Surgery, Mugla Sitki Kocman Medical School, Mugla, Turkey Funda Elibol Department of Radiology, Mugla Sitki Kocman Medical School, Mugla, Turkey E-mail address: [email protected]. Onder Ozcan Department of General Surgery, Mugla Sitki Kocman Medical School, Mugla, Turkey E-mail address: [email protected]. *
Conflict of interest statement There is no conflict of interest. Ethical approval
Corresponding author. Mugla Sitki Kocman University Medical School, Department of General Surgery, Mugla 48000, Turkey. E-mail address: [email protected] (A.K. Belli). 12 January 2015 Available online 26 February 2015
Ethical approval was not required. References [1] Obrist M, Osei-Bonsu E, Awuah B, Watanabe-Galloway S, Merajver SD, Schmid K, et al. Factors related to incomplete treatment of breast cancer in Kumasi, Ghana.
http://dx.doi.org/10.1016/j.breast.2015.02.003 © 2015 Elsevier Ltd. All rights reserved.
Prognosis of women with early breast cancer and PIK3CA mutations Sabine et al. (September 20 issue of Journal of Clinical Oncology) state that “PIK3CA mutations do not seem to affect residual risk following treatment with endocrine therapy” [1]. The Authors argue that there is a complex relationship between risk of recurrence and PIK3CA mutations since PIK3CA mutations are associated with multiple low-risk prognostic features in early breast cancer. Prognostic significance of PIK3CA activation has been widely analyzed in the scientific literature and PIK3CA somatic mutations
were never linked to poor prognosis [2]. This means the data reported by Sabine et al. are not striking as stated by the Authors. If we look instead at abnormal activation of the PI3K/Akt/mTOR pathway in germ cells we immediately realize it drives hamartoma growth. Of note hamartoma syndromes are manifested by benign tumors in multiple organs, nevertheless affected individuals have an increased risk of developing certain malignant cancers, and they usually also have a decreased life span compared to the
284
Letters to the Editor / The Breast 24 (2015) 283e284
general population [3]. Whether the role of PIK3CA mutations rises in a further phase by selective pressure (which could be also dependent on oncologic treatment) also in the somatic mutations setting is yet to be explored. For this purpose it would be useful to compare mutation positive and mutation negative patients regarding overall survival data in the Authors' database. In addition, the PI3K pathway is complex and it is now known that not only the mutations of the kinase, but also the loss of negative regulators such as PTEN and the expression of growth factors matter in the regulation of this route [4]. A limit of the analysis of a single marker is therefore represented by the fact that the control (i.e. the population without the marker of interest) has other factors involved in the activation of the pathway. To overcome this problem, it might be useful to deepen the analysis of the pathway with alternative techniques as stated by the Authors. Alternatively, a greater characterization of the population affected by the mutations can be attempted. The logistic regression analysis of prognostic factors shown by Sabine et al. is of great help, but it would be more interesting and with several direct clinical implication a tentative analysis of the distribution of mutations and the corresponding prognosis in pre-defined groups of patients, in particular in patients with variable expression of hormone receptors. The Authors comment that the kinase mutations are more frequently associated with the expression of PgR. Perhaps the data should be read in reverse, meaning that patients with mutations in the helical domain have more luminal B phenotype than the remaining patients. A much more important issue for patients with breast cancer is whether a relationship exists between PIK3CA mutations and benefit with a specific type of therapy. Yet, PIK3CA mutations have been reported to confer resistance to endocrine therapy [5]. Counterintuitively, the data by Sabine et al. go in the opposite direction. In order to interpret this data, we would like to point out that recent studies have shown that loss of PIK3CA mutations after neoadjuvant chemotherapy selects patients with better prognosis [6]. If patients treated within the TEAM study have differential response to chemotherapy based on the presence of mutations in PIK3CA this has to be taken into account, because the lack of difference in outcome between wild type and mutated PIK3CA patients
http://dx.doi.org/10.1016/j.breast.2015.02.028 © 2015 Elsevier Ltd. All rights reserved.
compared to hormonal therapy might be offset by an increased sensitivity to chemotherapy. We hope that current research on PI3K signaling will shed some additional light on the aforementioned topics.
References [1] Sabine VS, Crozier C, Brookes CL, Drake C, Piper T, van de Velde CJH, et al. Mutational analysis of PI3K/AKT signaling pathway in tamoxifen exemestane adjuvant multinational pathology study. J Clin Oncol 2014;32:2951e9. [2] Pang B, Cheng S, Sun SP, An C, Liu ZY, Feng X, et al. Prognostic role of PIK3CA mutations and their association with hormone receptor expression in breast cancer: a meta-analysis. Sci Rep 2014;4:6255. [3] Orloff MS, He X, Peterson C, Chen F, Chen JL, Mester JL, et al. Germline PIK3CA and AKT1 mutations in Cowden and Cowden-like syndromes. Am J Hum Genet 2013;92:76e80. [4] Vivanco I, Sawyers CL. The phosphatidylinositol 3-Kinase AKT pathway in human cancer. Nat Rev Cancer 2002;2:489e501. [5] Crowder RJ, Phommaly C, Tao Y, Hoog J, Luo J, Perou CM, et al. PIK3CA and PIK3CB inhibition produce synthetic lethality when combined with estrogen deprivation in estrogen receptor-positive breast cancer. Cancer Res 2009;69: 3955e62. [6] Jiang YZ, Yu KD, Bao J, Peng WT, Shao ZM. Favorable prognostic impact in loss of TP53 and PIK3CA mutations after neoadjuvant chemotherapy in breast Cancer. Cancer Res 2014;74:3399e407.
Serena Di Cosimo*, Giulia Valeria Bianchi, Giacomo Bregni, Filippo de Braud Department of Oncology, Istituto Nazionale dei Tumori, Milano, Italy *
Corresponding author. Department of Oncology, Istituto Nazionale dei Tumori, Via Venezian 1, 20133 Milano, Italy. Tel.: þ39 02 2390 3066; fax: þ39 02 2390 2049. E-mail address: [email protected] (S. Di Cosimo). 24 November 2014 Available online 12 March 2015
