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INTRODUCTION
Breast Cancer (BC) is recognized as the most commonly diagnosed neoplasm among female populations globally, with more than 2 million new cases documented in the year 2020. Where, the risk measurement associated with BC include both modifiable and non-modifiable factors, with nearly eighty percent of cases presenting in individuals aged over 50 years. The prognostic outcomes are significantly affected by both the stage of the cancer and its specific molecular subtype (Lukasiewicz et al., 2021). The diagnosis of the BC is done by physical examination, breast imaging (mammography) and tissue biopsy, whereas the treatment options currently used in clinical practice includes surgery, chemotherapy, Radiation Therapy (RT), hormonal therapy, and immunotherapy are being used (Watkins, 2019; Waks and Winer, 2019). For non-metastatic breast cancer surgery considered to be the most effective treatment and also, the chemotherapy-based preoperative systemic therapy decreases the tumour mass, prevents removal of axillary lymph nodes and conserve breast tissue. However, in metastatic BC, surgery is the first choice of treatment chemotherapy, RT, targeted therapy, immunotherapy, and hormonal therapy are used as palliative therapies (Cardoso et al., 2019; Senkus and Lacko, 2017). RT is one of the palliative therapies and reduces the relapse rate by fifty percent, where external beam radiation, brachytherapy, or both are being used (Litiere et al., 2012; Tang et al., 2018). Many studies reported that the comparison of various RT in adjuvant therapy as Whole Breast Irradiation (WBI), Partial Breast Irradiation (PBI), Accelerated partial-breast irradiation (APBI) and brachytherapy resulted in local relapse rate of 4.4 to 4.5% (Wang and Wu, 2023). However, the External Radiation Therapy (ERT) or External Beam therapy (EBT) can be used for irradiating the specific cancer tissues, where a low beam of protons or photons or electrons are used to kill tumour tissue and had been associated with promising results in BC, Prostate cancer etc. (Hanks, 1986). The adverse effects associated irradiating the breast tissue includes major coronary events such as atherosclerosis and even more worsening the condition in cardiovascular disease patients (Darby, 2013). pneumonitis in patients receiving nodal RT worsened by concomitant use of taxanes (Whelan et al., 2015; Brown et al., 2015). fibrosis of the irradiated breast tissue within 4-12 months of the RT (Williams et al., 2019). others including lymphadenoma, rib fracture and other RT induced secondary malignancies such as lung, and oesophageal cancers (Gross et al., 2019; Pierce et al., 1992; Ye et al., 2015). Management of RT associated adverse effects is carried out by maintaining oral hygiene, topical analgesics, dietary modification, opioid analgesics, chlorhexidine rinses, enteral tube feeding in severe cases (Majeed and Gupta, 2025). Thus, this study aimed to assess, report and management of Adverse events associated with Radiation therapy or Chemo-radiation therapy in breast cancer treatment.
METHODOLOGY
Study Design and Study Settings
This prospective observational study was conducted in accordance with ethical guidelines and IEC at Bharath Hospital and Institute of Oncology, Mysore, over a period of one Year. It aimed to assess radiation-related adverse events in breast cancer patients, using MedDRA codes for events, RTOG grades for severity, and evaluating their management during radiation therapy for Breast cancer treatment.
Study Participants Criteria
The study participants were selected based on specific inclusion and exclusion criteria. The inclusion criteria included patients receiving radiation therapy for breast cancer treatment, patients receiving radiation therapy and chemotherapy concomitantly, On the other hand, the exclusion criteria included patients without cancer, patients who are mentally challenged, and patients receiving no RT. By applying these criteria, the study aimed to ensure that the participants were relevant to the research question and that the results would be applicable to the targeted population.
Sampling Techniques and Sample Size Calculation
A prospective random sampling method was applied, and the sample size was calculated to enrol minimum of 312 participants, based on a 5% margin of error, 50% population proportion, 0.05 precision, and a 95% confidence interval, considering a 28% prevalence of breast cancer in India (Sathishkumar et al., 2024).
Data Collection and Data Analysis
Data were collected from various sources, including patient records, radiation charts, and laboratory reports, to obtain details on demographics, diagnosis, treatment plans, radiation dose and frequency, and medical history (File: S1). Patient interviews captured treatment experiences and adverse events, while discussions with oncologists and other healthcare professionals provided additional clinical insights and then Data is entered in to Microsoft Excel and analysed using SPSS v25.0 (IBM). Categorical variables were summarized as frequencies and percentages.
Study Procedure
Patients monitored daily for radiation-related adverse events. Identified events were verified with radiation oncologists to ensure accuracy and graded the events based on Radiation Therapy Oncology Group (RTOG) criteria. Management approaches and outcomes were reviewed to evaluate treatment effectiveness and highlight potential areas for improvement.
Ethical Approval
The study was conducted in accordance with Institutional Human Ethics Guideline. Duly signed of written Informed Consent form (File: S2) by patients in which are involved with no patient’s interventions. Ethical approval was obtained from the Institutional Ethics Committee, Bharath Hospital and Institute of Oncology (BHIO), Mysore. (File: S3).
RESULTS
Demographics Characteristics
A total of 315 breast cancer cases were reviewed in this study, all of which involved female patients. The largest proportion belonged to the 51-60 year age group (51.74%), followed by 40-50 years (28.25%). Only 6.05% of patients were younger than 40, while 13.96% were aged between 61 and 70 years. With respect to histopathology, invasive ductal or carcinoma was identified as the leading subtype (62.22%). Invasive lobular carcinoma accounted for 24.44%, and medullary breast carcinoma for 13.33%.
An evaluation of hormone and genetic receptor patterns showed that nearly half of the tumors were estrogen receptor positive (46.03%). A smaller fraction (3.80%) were estrogen receptor negative. Combined ER and PR positivity was recorded in 23.39%, while HER2 positivity occurred in 15.55% of cases. Tumors with triple receptor positivity represented 3.17%, whereas triple-negative cancers made up 5.39%. Additionally, 2.53% of patients had BRCA1 positivity.
When staged according to the TNM classification, the majority were detected in early disease (Stage 0-I, 60.3%). Approximately 21.3% were diagnosed with Stage II disease, while 8.23% had Stage III involvement. A notable 13.3% of patients were already at the metastatic stage (Stage IV) at presentation.
In summary, the study highlights that most patients were middle-aged women, with IDC being the most common histological type, and a predominantly hormone receptor-positive profile. Although many were diagnosed in the early stages, a considerable share of cases presented at an advanced or metastatic stage. Shown in Table 1.
| VARIABLES | FREQUENCY | PERCENTAGE | ||
|---|---|---|---|---|
| Age | ||||
| 29 to 39 years | 19 | 6.05% | ||
| 40 to 50 Years | 89 | 28.25% | ||
| 51 to 60 Years | 163 | 51.74% | ||
| 61 to 70 Years | 44 | 13.96% | ||
| Gender | ||||
| Male | 0 | 0% | ||
| Female | 315 | 100% | ||
| TPYE OF BREAST CANCER | ||||
| IDC/IFDC | 196 | 62.22% | ||
| ILC | 77 | 24.44% | ||
| MBC | 42 | 13.33% | ||
| DETAILS OF HORMONAL RECEPTOR | ||||
| ER +ve | 145 | 46.03% | ||
| ER -ve | 12 | 3.80% | ||
| ER/PR +ve | 74 | 23.39% | ||
| HER2 +ve | 49 | 15.55% | ||
| ER+PR+HER +ve (Tripple +ve) | 10 | 3.17% | ||
| ER+PR+HER -ve (Tripple -ve) | 17 | 5.39% | ||
| BRCA1 +ve | 8 | 2.53% | ||
| STAGE OF BREAST CANCER | ||||
| Stage | TNM | Number | % | |
| Stage 0 (DCIS) | Tis N0 M0 | 56 | 17.77% | |
| Stage IA | T1 N0 M0 | 89 | 28.26% | |
| Stage I B | T1N1mi M0 | 45 | 14.28% | |
| Stage II A | T1 N1M0 | 5 | 1.58% | |
| T2 N0 M0 | 3 | 0.95% | ||
| Stage II B | T2 N1 M0 | 31 | 9.84% | |
| T3 N0 M0 | 27 | 8.57% | ||
| Stage III A | T2 N2 M0 | 6 | 1.9 | |
| T3 N2 M0 | 7 | 2.22 | ||
| Stage IIIB | T4 N2 M0 | 9 | 2.85% | |
| Stage IIIC | T4 N3 M0 | 4 | 1.26% | |
| Stage IV | T4 N2 M1 | 19 | 6.03% | |
| T4 N3 M1 | 23 | 7.3 | ||
| TRAETMENT MODALITIES | ||||
| Types of Therapy | Radiation Therapy | Chemoradiation Therapy | Radiation with Targeted/Hormonal | Total n=315 |
| Adjuvant Therapy | 95 | 69 | 28 | 192 |
| Neo Adjuvant Therapy | 38 | 31 | 13 | 81 |
| Palliative Care | 15 | 19 | 8 | 42 |
| TYPE OF RADIATION THERAPY USED | ||||
| External beam radiation therapy | 248 | 78..73% | ||
| Brachy therapy | 67 | 21.26% | ||
| TYPE OF REGIMENS USED | ||||
| Regimens | Type of Therapy | |||
| AC+ PACLI (Adriamycin, Cyclophosphamide and Paclitaxel) | Chemotherapy | |||
| EC (Epirubicin, Cyclophosphamide) | ||||
| TC (Docetaxel and Cyclophosphamide) | ||||
| TAC (Docetaxel, Doxorubicin, Cyclophosphamide) | ||||
| PACLI (Paclitaxel) | ||||
| CARBO Pacli Carboplatin+ Paclitaxel) | ||||
| Capecitabine | ||||
| Olaparib | ||||
| ERIBULIN | ||||
| TRASTU (Trastuzumab) | Targeted Therapy | |||
| Pertuzumab | ||||
| Fulvestarant | Hormonal Therapy | |||
| Letrozole | ||||
| Anastrozole |
Treatment Modalities
Among 315 breast cancer patients, adjuvant therapy was the most frequently employed treatment approach (60.95%), followed by neoadjuvant (25.71%) and palliative therapy (13.33%). Within the adjuvant setting, radiation therapy alone was most common, while chemoradiation and radiation combined with targeted or hormonal therapy were also utilized. Similar patterns were observed in neoadjuvant and palliative groups, with radiation remaining the dominant modality.
External Beam Radiation Therapy (EBRT) constituted the principal technique, administered in 78.73% of cases, whereas brachytherapy was used in 21.26%. Chemotherapy regimens most often included AC+Paclitaxel (Adriamycin, Cyclophosphamide, and Paclitaxel), EC (Epirubicin and Cyclophosphamide), TC (Docetaxel and Cyclophosphamide), and TAC (Docetaxel, Doxorubicin, and Cyclophosphamide). Additional agents such as Capecitabine, Olaparib, and Eribulin were prescribed selectively in advanced or resistant cases. Targeted therapies comprised Trastuzumab and Pertuzumab, while hormonal agents included Fulvestrant, Letrozole, and Anastrozole. Shown in Table 1.
MedDRA Code and RTOG Grade of Radiation Therapy Adverse Events and their Management
In the present study involving 315 breast cancer patients, the most frequently reported radiation-associated adverse event was fatigue (73.96%), followed by dermatitis or skin reactions (42.85%), breast pain and swelling (31.11%), nausea (16.19%), gastritis (16.19%), hyperpigmentation (8.57%), and radiation pneumonitis (6.03%).
Fatigue, predominantly classified as RTOG Grade 1 (50.79%), was effectively managed with supportive fluid therapy such as 5% dextrose and DNS, while higher grades required multivitamin supplementation. Dermatitis was mainly of Grade 2 severity (60.74%) and responded well to topical Metronidazole with Gentian violet paint. Grade 3 cases were treated with Diclofenac and Lignocaine gel. Breast pain and swelling were primarily mild (Grade 1, 58.16%) and controlled with Diclofenac gel, whereas moderate to severe grades required Tramadol, Paracetamol, and Prednisolone combinations.
Nausea (16.19%) occurred across Grades 1-3 and was treated with Domperidone or Ondansetron depending on severity. Hyperpigmentation, mainly of Grade 3 (55.55%), was managed using topical agents containing Hydroquinone, Tretinoin, Fluocinolone acetonide, Kojic acid, and plant-based extracts. Gastritis was noted in 16.19% of patients, with Pantoprazole, Metoclopramide, and antacid suspensions (Oxethazine, Magnesium hydroxide, Aluminum hydroxide) used according to grade. Radiation pneumonitis (6.03%), mostly of Grade 1, was managed with Amifostine, while higher grades were treated with Methylprednisolone and Clarithromycin.
This study found the majority of adverse events were mild to moderate (RTOG Grades 1-2) and managed successfully with supportive or symptomatic therapy. Only a small proportion of patients required escalation to pharmacological interventions for Grade 3-4 toxicities, indicating that radiation therapy was generally well tolerated in this cohort. Shown in Table 2.
| MedDRA Code | Event | Number N=315/% | RTOG Grade | n (%) | Treatment | n (%) | No treatment received n (%) |
|---|---|---|---|---|---|---|---|
| 10016256 | Fatigue | 233 (73.96) | 1 | 160 (50.79) | 5% Dextrose | 131 (81.87) | 29 (18.12) |
| 2 | 52 (22.31) | DNS | 39 (75.0) | 13 (25.0) | |||
| 3 | 16 (6.86) | DNS + Multivitamin | 16 (100) | 0 | |||
| 4 | 5 (2.14) | RL + DNS + Multivitamin | 5 (100) | 0 | |||
| 10037867 | Dermatitis/ Change in Skin | 135 (42.85) | 1 | 32 (23.70) | Gentian violet Paint | 25 (78.12) | 7 (21.87) |
| 2 | 82 (60.74) | Metronidazole + Gentian violet Paint | 71 (86.58) | 11 (13.41) | |||
| 3 | 21 (15.55) | Diclofenac and lignocaine gel | 21 (100) | 0 | |||
| 10006477 | Breast Pain and Swealing | 98 (31.11) | 1 | 57 (58.16) | Diclofenac Gel | 37 (64.91) | 20 (35.08) |
| 2 | 29 (29.59) | Diclofenac + Lignocaine gel Tab. Aceclofenac | 29 (100) | 0 | |||
| 3 | 12 (12.24) | Diclofenac + Lignocaine Gel, Tab. Tramadol + Paracetamol + Prednisolone | 12 (100) | 0 | |||
| 1002813 | Nausea | 54 (16.19) | 1 | 23 (42.59) | Tab. Domperidone | 18 (78.26) | 5 (21.73) |
| 2 | 18 (33.33) | Inj. Ondansetron | 15 (83.33) | 3 (16.66) | |||
| 3 | 13 (24.07) | Inj. Ondansetron | 13 (100) | 0 | |||
| 10020673 | Hyperpig-mentation | 27 (8.57) | 1 | 7 (25.92) | Hydroquinone USP + Tretinoin USP + Fluocinolone Acetonide | 4 (57.14) | 3 (42.85) |
| 2 | 5 (18.51) | Hydroquinone USP + Tretinoin USP + Fluocinolone Acetonide | 5 (100) | 0 | |||
| 3 | 15 (55.55) | Kojic Acid Dipalmitate + Arbutin + Liquorice, Mulberry Extract+ Tetrahydrocurcumin + Artocarpus Extract | 11 (73.33) | 4 (26.66) | |||
| 10019350 | Gastritis | 51 (16.19) | 1 | 14 (27.45) | Tab. Pantoprazole | 9 (64.28) | 5 (35.71) |
| 2 | 17 (33.33) | Tab. Pantoprazole + Metoclopramide | 13 (76.47) | 4 (23.52) | |||
| 3 | 12 (23.52) | Tab. Pantoprazole, Susp. Oxethazine, Mg (OH)2, Al (OH)3 | 12 (100) | 0 | |||
| 4 | 8 (15.68) | Inj. Pantoprazole, Susp. Oxethazine, Mg (OH)2, Al (OH)3 | 8 (100) | 0 | |||
| 10020405 | Radiation Pneumonitis | 19 (6.03) | 1 | 14 (73.68) | Tab. Amifostine | 14 (100) | 0 |
| 2 | 5 (26.31) | Tab. Methyl Prednisolone, Tab. Clarithromycin | 5 (100) | 0 |
Interventions and Supportive Care in Untreated Adverse Events
Evaluation of patients lacking management for radiation-related toxicities revealed notable care deficiencies. Approximately 18-25% with fatigue, 13-22% with dermatitis, and about 35% experiencing breast pain or swelling did not receive therapy. Likewise, 16-35% of those with nausea or gastritis and up to 43% with hyperpigmentation were left untreated. In contrast, all radiation pneumonitis cases were properly addressed. The highest gaps occurred in fatigue and breast pain, highlighting the need for prompt assessment and affordable supportive measures. Enhancing pharmacist-driven and team-based care, alongside standardized management guidelines, could reduce untreated cases and improve patient outcomes. Shown in Table 2.
DISCUSSION
Most breast cancer patients receiving radiation therapy were middle-aged women with invasive ductal carcinoma and hormone receptor-positive tumors, consistent with previous reports by (DeSantis et al., 2019; Sung et al., 2021). Radiation therapy remains vital for disease control and survival improvement (Darby et al., 2013). Though its benefits are often limited by treatment-related toxicities. Fatigue and dermatitis were the most common adverse events, in line with earlier studies (Schnur et al., 2011; Kole and Moran, 2017). Most were mild to moderate (RTOG Grades 1-2) and effectively managed with supportive care, indicating advances in radiation techniques. However, some patients did not receive appropriate management for fatigue, skin reactions, or breast pain, suggesting a need for improved follow-up and supportive care. Active involvement of pharmacists and nursing staff, as emphasized by (Holle, 2020), may enhance timely toxicity management. Less frequent events such as gastritis, hyperpigmentation, and pneumonitis were also observed, with pneumonitis requiring close monitoring due to respiratory risk, as noted by (Palma et al., 2013). Therefore, systematic toxicity grading, early intervention, and multidisciplinary monitoring can improve radiation tolerability and patient quality of life.
CONCLUSION
Radiation therapy in breast cancer patients was well tolerated, with most toxicities being mild or moderate and effectively managed through supportive measures. Patients on radiation and chemo radiation therapy need careful follow up to identify radiation related negative outcomes. However, the presence of untreated or inadequately addressed adverse events highlights the need for proactive supportive care. Integrating multidisciplinary interventions particularly pharmacist-led management can strengthen symptom control, improve treatment adherence and enhance the patient’s overall quality of life. Continuous toxicity monitoring and patient counselling should be integral parts of radiation therapy programs.