DISCUSSION

In this retrospective study of 214 consecutive TNBC patients treated with radiation therapy at an Australian regional cancer center, we sought to determine whether differing treatment regimens (chemotherapy, radiation technique, fractionation protocol, type of surgery) affected survival outcomes and secondly, whether clinical characteristics were significant predictors of survival. Chemotherapy usage, radiotherapy technique and fractionation schedule, and type of surgery were not associated with DFS or OS in this patient cohort. However, nodal involvement was linked to significantly poorer DFS and OS while tumor size was the only predictor of poorer OS.

The role of breast-conserving surgery has been infrequently examined in TNBC patients. An analysis of the Surveillance, Epidemiology, and End Results (SEER) population-based database showed that breast-conserving surgery combined with radiation therapy was associated with better breast cancer-specific survival and OS compared to mastectomy.18 On multivariate analysis, advanced nodal status and tumor size were significant factors for adverse survival. A Chinese study of 308 patients, with immunohistochemically-confirmed TNBC, showed that breast-conserving surgery was not associated with increased ipsilateral tumor recurrence compared to a non-TNBC subtype cohort.19 A recent European study examined 71 TNBC patients after breast-conserving surgery and intraoperative boost radiotherapy with electrons (IOERT) followed by standard whole breast irradiation.20 After a median follow-up of 97 months (range 4–170 months), five in-breast recurrences were detected (7.0%). Eight year actuarial rates for local control, metastases-free survival, disease-specific survival, and overall survival were 89, 75, 80, and 69%, respectively. In our patients treated with breast-conserving surgery, mean DFS was 114 months; in contrast, patients receiving mastectomy had a mean DFS of 65.2 months (p<0.0001). While this difference was not significant in multivariate analysis, it is notable that the mastectomy group had more advanced disease: there were 26.1% of patients with T3 and above, versus 4.5% in the conserved group.


Continue Reading

Nodal status is one of the most important clinicopathological factors with prognostic significance in breast cancer.21 Nodal status has also been shown to be a prognostic factor for survival in TNBC in some22–25 but not all studies.26,27 In our study, lymph node negative TNBC was associated with better survival (both OS and DFS) than lymph node positive patients in univariate analysis, but the association did not apply for OS in subsequent multivariate analysis.

While there is a general trend in radiation oncology towards hypofractionation, the possible benefits and drawbacks of hypofractionated regimens in TNBC are unclear. In general, hypofractionation has been shown to deliver equivalent rates of local and locoregional control with equivalent or improved toxicity and cosmetic outcomes compared to conventional protocols.16,28 In our study, there appeared to be no worse outcomes for TNBC patients treated with the hypofractionated protocol with respect to both DFS and OS.

Although chemotherapy was not a focus of this study, chemotherapy usage was included as a possible factor for survival in TNBC patients. Neoadjuvant and adjuvant chemotherapy are standard systemic treatment for early TNBC, and anthracycline and taxane-based chemotherapy regimens comprise the current standard of care.29 In our study, chemotherapy (neoadjuvant, adjuvant) was not a significant factor for DFS nor for OS. However, other studies have shown that standard adjuvant chemotherapy regimens improve overall survival in TNBC patients, for example, patients with T1/2 node-positive TNBC.10

Possible limitations to this study should be considered. As this was a retrospective study, follow-up times varied widely. Nevertheless, the periods of observation extended to over 100 months, which allowed for adequate follow-up of this aggressive phenotype. Selection bias was minimized by including all TNBC patients who had completed surgery, chemotherapy and radiation therapy at our institution. However, we have not attempted to include information on type of chemotherapy such as adjuvant or neoadjuvant chemotherapy, as a survival factor.

CONCLUSION

We have investigated the prognostic factors for survival in a cohort of TNBC patients treated at an Australian regional cancer center. Advanced disease exhibited by positive nodal status and larger tumor size was associated with poorer DFS. The type of radiotherapy technique and fractionation protocol were not associated with DFS or OS.

Acknowledgments

We thank Drs Carmen Hansen, Andrew Last and Julan Amalaseelan for access to their patients’ records.

Disclosure

The authors report no conflicts of interest in this work. This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sectors.


Shelly Wen,1,2 Lucy Manuel,1,2 Moira Doolan,1,2 Justin Westhuyzen,1 Thomas P. Shakespeare,1,2 Noel J. Aherne1,2

1Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour, New South Wales, Australia; 2University of New South Wales, Sydney, New South Wales, Australia

Correspondence: Noel J. Aherne
Department of Radiation Oncology, Mid North Coast Cancer Institute, Coffs Harbour NSW 2450, Australia
Tel +61-2-6656-7000
Fax +61-2-6656-5330
Email [email protected]


References

1. Australian Institute of Health and Welfare (AIHW). Australian Cancer Incidence and Mortality (ACIM) Books: All Cancers Combined. Canberra; 2017. Accessed February 12, 2017.

2. Onitilo AA, Engel JM, Greenlee RT, Mukesh BN. Breast cancer subtypes based on ER/PR and Her2 expression: comparison of clinicopathologic features and survival. Clin Med Res. 2009;7:4–13. doi:10.3121/cmr.2009.825

3. Carey L, Winer E, Viale G, Cameron D, Gianni L. Triple-negative breast cancer: disease entity or title of convenience? Nat Rev Clin Oncol. 2010;7:683–692. doi:10.1038/nrclinonc.2010.154

4. Oakman C, Viale G, Di Leo A. Management of triple negative breast cancer. Breast. 2010;19:312–321. doi:10.1016/j.breast.2010.03.026

5. Pal SK, Childs BH, Pegram M. Triple-negative breast cancer: unmet medical needs. Breast Cancer Res Treat. 2011;125:627–636. doi:10.1007/s10549-010-1293-1

6. Pal SK, Mortimer J. Triple-negative breast cancer: novel therapies and new directions. Maturitas. 2009;63:269–274. doi:10.1016/j.maturitas.2009.06.010

7. Naher S, Tognela A, Moylan E, Adams DH, Kiely BE. Patterns of care and outcomes among triple negative early breast cancer patients in South Western Sydney. Intern Med J. 2018;48:567–572. doi:10.1111/imj.13628

8. Kim JE, Ahn HJ, Ahn JH, et al. Impact of triple-negative breast cancer phenotype on prognosis in patients with stage I breast cancer. J Breast Cancer. 2012;15:197–202. doi:10.4048/jbc.2012.15.2.197

9. MacBride MB, Neal L, Dilaveri CA, et al. Factors associated with surgical decision making in women with early-stage breast cancer: a literature review. J Womens Health (Larchmt). 2013;22:236–242. doi:10.1089/jwh.2012.3969

10. Kim HA, Seong MK, Kim EK, et al. Evaluation of the survival benefit of different chemotherapy regimens in patients with T1-2N0 triple-negative breast cancer. J Breast Cancer. 2015;18:271–278. doi:10.4048/jbc.2015.18.3.271

11. Keating NL, Landrum MB, Brooks JM, et al. Outcomes following local therapy for early-stage breast cancer in non-trial populations. Breast Cancer Res Treat. 2011;125:803–813. doi:10.1007/s10549-010-0865-4

12. EviQ Cancer Treatments Online. Breast invasive cancer adjuvant EBRT conventional whole breast. Last modified 28 April 2016. Available from: https://www.eviq.org.au/radiation-oncology/breast/1922-breast-invasive-cancer-adjuvant-ebrt-conventi. Accessed August 18, 2016.

13. EviQ Cancer Treatments Online. Breast invasive cancer adjuvant EBRT hypofractionation whole breast. Last modified 28 April 2016. Available from: https://www.eviq.org.au/radiation-oncology/breast/1923-breast-invasive-cancer-adjuvant-ebrt-hypofrac. Accessed August 18, 2016.

14. Cancer Australia. Recommendations for Use of Hypofractionated Radiotherapy for Early (Operable) Breast Cancer – A Clinical Practice Guideline. Surry Hills, NSW; 2015.

15. Shaitelman SF, Schlembach PJ, Arzu I, et al. Acute and short-term toxic effects of conventionally fractionated vs hypofractionated wholebreast irradiation: a randomized clinical trial. JAMA Oncol. 2015;1:931–941. doi:10.1001/jamaoncol.2015.2666

16. Nitsche M, Dunst J, Carl UM, Hermann RM. Emerging role of hypofractionated radiotherapy with simultaneous integrated boost in modern radiotherapy of breast cancer. Breast Care (Basel). 2015;10:320–324. doi:10.1159/000436951

17. Delaney GP, Gandhidasan S, Walton R, Terlich F, Baker D, Currow D. The pattern of use of hypofractionated radiation therapy for early-stage breast cancer in New South Wales, Australia, 2008 to 2012. Int J Radiat Oncol Biol Phys. 2016;96:266–272. doi:10.1016/j.ijrobp.2016.05.016

18. Chen Q-X, Wang -X-X, Lin P-Y, et al. The different outcomes between breast-conserving surgery and mastectomy in triple-negative breast cancer: a population-based study from the SEER 18 database. Oncotarget. 2017;8:4773–4780. doi:10.18632/oncotarget.13976

19. Wang L, Ouyang T, Wang T, et al. Safety of breast-conserving treatment for triple-negative breast cancer. Zhonghua Wai Ke Za Zhi. 2015;53:947–952.

20. Fastner G, Hauser-kronberger C, Moder A, et al. Survival and local control rates of triple-negative breast cancer patients treated with boost-IOERT during breast-conserving surgery. Strahlenther Onkol. 2016;192:1–7. doi:10.1007/s00066-015-0895-2

21. Wang -X-X, Jiang Y-Z, Li -J-J, Song C-G, Shao Z-M. Effect of nodal status on clinical outcomes of triple-negative breast cancer: a population-based study using the SEER 18 database. Oncotarget. 2016;7:46636–46645. doi:10.18632/oncotarget.9432

22. Steward L, Conant L, Gao F, Margenthaler JA. Predictive factors and patterns of recurrence in patients with triple negative breast cancer. Ann Surg Oncol. 2014;21:2165–2171. doi:10.1245/s10434-014-3546-4

23. Ovcaricek T, Frkovic SG, Matos E, Mozina B, Borstnar S. Triple negative breast cancer – prognostic factors and survival. Radiol Oncol. 2011;45:46–52. doi:10.2478/v10019-010-0054-4

24. Rakha EA, El-sayed ME, Green AR, Lee AH, Robertson JF, Ellis IO. Prognostic markers in triple-negative breast cancer. Cancer. 2007;109:25–32. doi:10.1002/cncr.22381

25. Liao GS, Chou YC, Hsu HM, Dai MS, Yu JC. The prognostic value of lymph node status among breast cancer subtypes. Am J Surg. 2015;209:717–724. doi:10.1016/j.amjsurg.2014.05.029

26. Nishimura R, Arima N. Is triple negative a prognostic factor in breast cancer? Breast Cancer. 2008;15:303–308. doi:10.1007/s12282-008-0042-3

27. Shibuta K, Ueo H, Furusawa H, et al. The relevance of intrinsic subtype to clinicopathological features and prognosis in 4266 Japanese women with breast cancer. Breast Cancer. 2011;18:292–298. doi:10.1007/s12282-010-0209-6

28. Haviland JS, Owen JR, Dewar JA, et al. The UK Standardisation of Breast Radiotherapy (START) trials of radiotherapy hypofractionation for treatment of early breast cancer: 10-year follow-up results of two randomised controlled trials. Lancet Oncol. 2013;14:1086–1094. doi:10.1016/S1470-2045(13)70386-3

29. Park JH, Ahn J-H, Kim S-B. How shall we treat early triple-negative breast cancer (TNBC): from the current standard to upcoming immuno-molecular strategies. ESMO Open. 2018;3(Suppl 1):e000357. doi:10.1136/esmoopen-2018-000357

Source: Breast Cancer: Targets and Therapy.
Originally published March 6, 2020.