A 48-year-old Brazilian woman (level of education = 7 years) was diagnosed with grade III invasive ductal carcinoma of the breast, involving lymph nodes. Her K-67 index, a marker indicating the percentage of tumor cells in the active phase of the cell cycle, was measured at 15%, reflecting a moderately high level of proliferation. The tumor was classified as estrogen receptor-positive (ER+) and progesterone receptor-positive (PR+), but negative for Human Epidermal growth factor Receptor-type 2 (HER2-), suggesting it might respond well to hormone therapy. She had no evidence of metastasis, indicating the disease was localized, and she had no history of previous cancer (Ibrahim et al., 2023; Wolff et al., 2023).

The participant had no history of neurological disorders, cardiovascular disease, head trauma, solvent exposure, or caffeine dependency/withdrawal that could affect visual processing or cognition. The participant was assessed for anxiety and depression symptoms at both time points using the Beck Depression Inventory (BDI-II) and the Beck Anxiety Inventory (BAI). The BDI-II is known for its high internal consistency, with a Cronbach's alpha value typically between 0.86 and 0.91 (Beck et al., 1996). The BAI similarly shows excellent internal consistency, with a Cronbach's alpha value ranging from 0.92 to 0.94 (Beck & Steer, 1990). The results suggested mild severity levels for depression and anxiety at both time points. Assessing depression and anxiety during cancer treatment is important because these psychological conditions can significantly affect overall well-being, treatment adherence, and even recovery outcomes (Abdelhadi, 2023; Almeida et al., 2023).

Laboratory tests were also evaluated before and after the antineoplastic treatments. The tests were performed by a reliable laboratory. When compared to the normative values for women (i.e., between 0.7 mg/d; Delanaye et al., 2023), only the creatinine values showed a slight alteration (i.e., 0.2 mg/dL) right after the chemotherapy treatment. Changes in creatinine levels after chemotherapy are typically reversible and usually do not have clinical implications if other indicators of renal function remain stable. Evidence suggests that these levels tend to normalize once treatment is completed and the patient has had time to recover (Jagieła et al., 2021). This result was reversed in the evaluation performed six months after the hormone therapy treatment (Table 1).

Table 1

Variable	Before Chemotherapy	After Chemotherapy	After Hormone Therapy
BDI-II score		18	17
BAI score		14	14
Glucose (mg/dL)	86	79	80
Creatinine (mg/dL)	0.5	0.2	0.5
AST/TGO (U/mL)	14	16	13
ALT/TGP (U/mL)	12	27	11
Red blood cells (millions/mm³)	4.0	3.4	4.0
Hemoglobin (g/dL)	12.5	11.6	12.5
Hematocrit (%)	37.2	33.3	37.4
Mean corpuscular volume (fL)	92.5	97.4	93.5
Mean corpuscular hemoglobin (pg)	31.1	33.9	31.3
Mean corpuscular hemoglobin concentration (g/dL)	33.6	34.8	33.4
Red cell distribution width (%)	12.7	12.9	12.4
Total leukocytes (cells/mm³)	6,600	4,800	5,800
Platelet count (cells/mm³)	224,000	244,000	173,000

Note. ALT = alanine aminotransferase; AST = aspartate aminotransferase; BAI = Beck Anxiety Inventory; BDI-II = Beck Depression Inventory-II; MCH = mean corpuscular hemoglobin; MCHC = mean corpuscular hemoglobin concentration; MCV = mean corpuscular volume; RDW = red cell distribution width.

The participant had no eye disease, according to self-reports and examinations performed in recent years. She was also screened for color blindness using Ishihara's pseudo-isochromatic plates (Ishihara, 1964) and did not have more than three errors (failure criterion) in the test (Fernandes et al., 2020). Finally, the participant had normal visual acuity (20/20), assessed using Raskin's E-optotypes.

The participant was mastectomized and initially submitted to chemotherapy treatment under intravenous administration of doxorubimycin 60mg/m², every 3 weeks, for 4 cycles. Subsequently, paclitaxel 80mg/m² was started once a week for 12 cycles. The first evaluation occurred one week after the administration of the last cycle of chemotherapy treatment. One month after the end of chemotherapy treatment, the participant started hormone therapy. The second evaluation occurred after six consecutive months of administration of tamoxifen 20 mg/day.

We present a case report of a woman with breast cancer indicating changes in visual processing after antineoplastic treatment. Figure 1 shows the spatial contrast sensitivity function for the research participant after receiving chemotherapy and after six months of daily treatment with hormone therapy. The solid line represents the test values for chemotherapy and the dotted line represents the test values for hormone therapy. Each data point represents the participant's contrast threshold. The acronym cpg stands for cycles per degree of visual angle.

Figure 1

The participant demonstrated a change in the sensitivity curve in both test conditions, compared to normative values suggested in the literature (Fernandes et al., 2019). However, we can see a slight improvement in some spatial frequencies (0.6; 3.1; 8.8; 13.2; 15.6) at the second time point, even under daily administration of hormone therapy, suggesting better test performance at the second time point.

The results presented suggest a change in contrast sensitivity for all spatial frequencies at both time points when compared to the normative data presented in the literature (Fernandes et al., 2019). In addition, the results disagree with the CSF presented in previous studies, where at photopic luminance levels maximum contrast sensitivity occurs at medium frequencies, with reduced sensitivity at the extremes of the curves (Adams & Courage, 2002).

Evidence suggests that worsening sensitivity at medium and high spatial frequencies can occur in individuals subjected to diseases or medications that can interfere with brain function (Campbell & Maffei, 1974; Roudaia et al., 2010; Sekuler & Tynan, 1977). Despite the slight improvement shown in some spatial frequencies six months after chemotherapy, the results are still incipient and controversial, and this may be due to the short comparison time between the two results. Therefore, it is important that these results be interpreted with caution.

The bar graphs present the results obtained for the three vectors, Protan, Deutan, and Tritan, for the participant who underwent chemotherapy treatment and then, six months later, received hormone therapy treatment (Figure 2). In the graph, the bars represent the test values for chemotherapy and hormone therapy. The top of the bar represents the participant's color discrimination threshold at these time points.

Note. The

The results suggest greater sensitivity to protan, deutan, and tritan axes in the research participant six months after completion of chemotherapy treatment, with daily administration of hormone therapy. Studies investigating the sensitivity to chromatic contrast in women with breast cancer are still scarce. However, changes in color perception have been suggested in breast cancer patients undergoing FAC (5-fluorouracil, adriamycin and cyclophosphamide) chemotherapy regimen. Chromatic sensitivity improved four months after the evaluation (Giralt et al., 2012).

Regarding achromatic contrast vision, the participant showed less sensitivity to distinguish objects in low contrast for low, medium, and high spatial frequencies. Women with breast cancer being treated with doxorubicin and paclitaxel may have alterations in the M and P pathways, or in retinal receptor cells (Lee et al., 2000). Similar results have been presented in the literature in women who had received chemotherapy using the FAC system (Santos et al., 2011).

There is evidence that chemotherapy can trigger changes in nerve cells present in the primary visual cortex (Jansen et al., 2005). In addition, ocular toxicity associated with chemotherapy treatment has been reported in the literature (Anderson et al., 2020; Raffa & Tallarida, 2010). Alterations in normal brain physiology induced by drugs such as doxorubimicin and paclitaxel can occur through pro-inflammatory cytokines, which are considered immune cells that are activated in response to inflammation, stress, or direct damage to neurons (Maier & Watkins, 2003). Studies suggest that chemotherapy is related to mitochondrial dysfunction and increased levels of pro-inflammatory cytokines (IL-1b, IL-6, TNF-a, IL-10), leading to peripheral neuropathy as well as impairment of functions involving the frontal lobe (Lomeli et al., 2017; Lyon et al., 2016; Polomano et al., 2001).

Glial cells synthesize and release IL-1, IL-6 and TNF-D (Hopkins & Rothwell, 1995). The interaction between neurons and glial cells in the CNS can facilitate regeneration or neuronal damage, triggering deficiencies in neurotransmitters such as acetylcholine or dopamine, thus contributing to cognitive changes (Ahles & Saykin, 2007; Wilson & Humanski, 1993). Dopaminergic amacrine cells present in the retina are sensitive to luminance contrast (Burkhardt & Fahey, 1999). Therefore, deficits in dopamine neurotransmitters can generate changes in contrast sensitivity.

The relationship between tamoxifen uses and the occurrence of retinopathy and keratopathy is well established in the literature (Noureddin et al., 1999; Pavlidis et al., 1992). However, the length of time of drug use necessary to generate ocular toxic effects is still a source of disagreement (Eisner & Incognito, 2006; Kaiser-Kupfer & Lippman, 1978; Noureddin et al., 1999; Salomão et al., 2007). While some studies suggest that the short time of tamoxifen use (< 2 years) is sufficient to generate ocular toxicity, other studies suggest the importance of higher cumulative doses for evidence of retinal abnormality (Eisner & Incognito, 2006; Salomão et al., 2007). This is because sustained administration of endocrine medications has the potential to increase the risk or severity of several age-related eye diseases or conditions, including among breast cancer survivors undergoing treatment (Oliveira et al., 2023).

Studies have been conducted to determine whether standard doses of hormone therapy drugs affect wavelength-mediated visual sensations via cones. Some cases of loss of color vision suggest that the drug may cause functional damage to the inner layers of the retina (Salomão et al., 2007). Thus, it is considered that the use of tamoxifen may affect some neural functions of the visual system (Eisner, 2004; Salomão et al., 2007).

Evidence indicates that estrogenic activity directly influences physiological functions (Burstein et al., 2019). Estrogen receptors (ERs) are distributed throughout the human body, including ocular structures like the bulbar conjunctiva, tarsal plates, lacrimal glands, lens, and cornea (Spelsberg et al., 2004). Additionally, ERs are present in the CNS (Morissette et al., 2008). Thus, changes in estrogenic activity may affect both central and ocular visual processing (Eisner & Luoh, 2011).

This study presents some limitations. The fact that the evaluation was carried out with only one participant diminishes the power of the results presented, making it impossible to stratify the results for other realities. However, the importance of the study in the search for controlling intervening variables presented in the population of interest should be considered. One of the difficulties found in previous studies was the lack of control by type of cancer and by medication used, since several drugs are administered during the antineoplastic treatment. In this regard, we sought to control for the interaction between the drugs used.

An improvement in the sensitivity curves was shown six months after the end of chemotherapy treatment (Figure 1, Figure 2). In this regard, it is important to consider that the functional measures improved somewhat, although we cannot draw any conclusions about this, especially since the period between the administration of chemotherapy and hormone therapy was very close (6 months).

The results presented suggest further research on how different cortical areas involved in spatial vision may be adversely affected by these clinical conditions. The tests used are considered very rigorous and useful clinical tools for assessing basic visual functions, as well as visual pathways from the retina to the visual cortex. Therefore, this finding may assist research in the fields of oncology and neuroscience.

Further investigations, especially with a larger sample size, are needed to elucidate the pathophysiological mechanisms that are involved in the changes presented. Such investigations would also help to determine to what extent chromatic and achromatic contrast sensitivity can serve as a biomarker of important aspects of breast cancer and its treatments.