ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ
Although highly penetrant genes such as BRCA1, BRCA2, TP53, PALB2, CHEK2, and ATM are well known in hereditary breast cancer, genes with low penetrance may also contribute to the disease risk. The CASR (Calcium-Sensing Receptor) gene, located on chromosome 3q13.3–q21, encodes a G-protein-coupled rec...
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Experimental Oncology| _version_ | 1868113233197400064 |
|---|---|
| author | Kitsera, N. Shparyk, Ya. Duda, I. Mylyan, Yu. Kunta, N. |
| author_facet | Kitsera, N. Shparyk, Ya. Duda, I. Mylyan, Yu. Kunta, N. |
| author_institution_txt_mv | [
{
"author": "N. Kitsera",
"institution": "Lviv Oncology Regional Treatment and Diagnostic Center, Lviv, Ukraine"
},
{
"author": "Ya. Shparyk",
"institution": "Lviv Oncology Regional Treatment and Diagnostic Center, Lviv, Ukraine"
},
{
"author": "I. Duda",
"institution": "Lviv Oncology Regional Treatment and Diagnostic Center, Lviv, Ukraine"
},
{
"author": "Yu. Mylyan",
"institution": "Lviv Oncology Regional Treatment and Diagnostic Center, Lviv, Ukraine"
},
{
"author": "N. Kunta",
"institution": "Danylo Halytskyi Lviv National Medical University, Lviv, Ukraine"
}
] |
| author_sort | Kitsera, N. |
| baseUrl_str | https://exp-oncology.com.ua/index.php/Exp/oai |
| collection | OJS |
| datestamp_date | 2026-06-15T10:40:08Z |
| description | Although highly penetrant genes such as BRCA1, BRCA2, TP53, PALB2, CHEK2, and ATM are well known in hereditary breast cancer, genes with low penetrance may also contribute to the disease risk. The CASR (Calcium-Sensing Receptor) gene, located on chromosome 3q13.3–q21, encodes a G-protein-coupled receptor that regulates calcium homeostasis and parathyroid hormone secretion. here we describe the clinical course and genetic findings in a breast cancer patient diagnosed with hER2-positive (hER2/neu +++) and ER/PR-negative infiltrating ductal carcinoma with a rare CASR mutation and explore its potential role in the hereditary breast cancer predisposition. Next-generation sequencing re- vealed a heterozygous CASR variant, c.2265G>t (p.Glu755Asp), classified as a variant of uncertain significance (VUS). No pathogenic mutations were found in BRCA1/2, CHEK2, or PALB2. The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant’s pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact. |
| doi_str_mv | 10.15407/exp-oncology.2026.01.066 |
| first_indexed | 2026-06-15T01:00:27Z |
| format | Article |
| fulltext |
66 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
CASE REPORT
C i t a t i o n: Kitsera N, Shparyk Ya, Duda I, Mylyan Yu, Kunta N. A case report of a rare CASR mutation associated with
HER2-positive breast cancer. Exp Oncol. 2026; 48(1): 66-72. https://doi.org/10.15407/exp-oncology.2026.01.066
© PH “Akademperiodyka” of the NAS of Ukraine, 2026. This is an open access article under the CC BY-NC-ND license
(https://creativecommons.org/licenses/by-nc-nd/4.0/)
Breast cancer (ВС) remains one of the most com-
monly diagnosed cancers in women worldwide.
The familial and hereditary components account
for approximately 5—10% of all BC cases. Muta-
tions in various genes can lead to the development
of BC by disrupting the regulation of cell growth,
division, and apoptosis. The most well-known of
these include BRCA1, BRCA2, TP53, PALB2,
CHEK2, and ATM, which are associated with he-
reditary forms of the disease [1, 2]. Additionally,
other genes with low or moderate penetrance may
also contribute to the BC risk, especially when
combined with the environmental factors [3].
The CASR (Calcium-Sensing Receptor) gene is
currently considered a low-penetrance gene and is
not classified among the major high-risk BC sus-
ceptibility genes [4, 5]. The CASR gene is located
on chromosome 3q13.3–q21. It encodes a G-pro-
https://doi.org/10.15407/exp-oncology.2026.01.066
N. Kitsera 1, 2, *, Ya. Shparyk 1, 3,
I. Duda 1, Yu. Mylyan 1, N. Kunta 3
1 Lviv Oncology Regional Treatment and Diagnostic Center, Lviv, Ukraine
2 Ivano-Frankivsk National Medical University, Ivano-Frankivsk, Ukraine
3 Danylo Halytskyi Lviv National Medical University, Lviv, Ukraine
* Correspondence: E-mail: nkitsera@gmail.com
A Case Report: A Rare Casr
Mutation Associated with
HER2-Positive Breast Cancer
Although highly penetrant genes such as BRCA1, BRCA2, TP53, PALB2, CHEK2, and ATM are well known in hereditary
breast cancer, genes with low penetrance may also contribute to the disease risk. The CASR (Calcium-Sensing Receptor)
gene, located on chromosome 3q13.3–q21, encodes a G-protein-coupled receptor that regulates calcium homeostasis
and parathyroid hormone secretion. Here we describe the clinical course and genetic findings in a breast cancer patient
diagnosed with HER2-positive (HER2/neu +++) and ER/PR-negative infiltrating ductal carcinoma with a rare CASR
mutation and explore its potential role in the hereditary breast cancer predisposition. Next-generation sequencing re-
vealed a heterozygous CASR variant, c.2265G>T (p.Glu755Asp), classified as a variant of uncertain significance (VUS).
No pathogenic mutations were found in BRCA1/2, CHEK2, or PALB2. The patient underwent neoadjuvant chemothera-
py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur-
rence after ten months of follow-up. Although the CASR p.Glu755Asp variant’s pathogenic role is unproven, emerging
evidence links CASR overexpression with HER2-positive breast cancers, promoting tumor progression via calcium-
dependent signaling pathways (PI3K/AKT, MAPK). This case highlights the potential role of CASR as a low-penetrance
susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact.
Keywords: breast cancer, family history, CASR gene mutation, HER2+++, trastuzumab, Ukraine.
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 67
A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer
tein-coupled receptor that plays a pivotal role in
maintaining calcium homeostasis by regulating
parathyroid hormone (PTH) secretion and renal
calcium reabsorption [6]. The pathogenic muta-
tions in CASR are associated with such conditions
as familial hypocalciuric hypercalcemia (FHH), fa-
milial isolated hyperparathyroidism, chronic pan-
creatitis, and idiopathic generalized epilepsy [7].
This report aims to describe the clinical course
and genetic findings in a BC patient with a rare
CASR gene mutation and to explore the potential
role of CASR in hereditary BC predisposition.
Case presentation
Patient C., a 50-year-old woman from a small town
in Ukraine, presented with symptoms in May 2022
and was diagnosed with BC in June 2022. On May
31, 2022, a core needle biopsy of the breast was per-
formed. The histology report (No. 26305), dated
June 1, 2022, confirmed the infiltrating Grade 2
(G2) ductal carcinoma. The immunohistochemis-
try results, dated June 09, 2022, showed that the
estrogen receptor (ER) and progesterone receptor
(PR) were negative, c-erbB2 (Her2/neu) was
strongly positive (+++), and the Ki-67 proliferation
index was 20%. The chest X-ray, dated May 30,
2022, and the hepatobiliary ultrasound, dated June
01, 2022, revealed no malignant lesions. The heart
ultrasound performed on June 13, 2022, showed
the heart chambers to be within normal limits. The
global segmental contractility was preserved. No
pathological abnormalities were detected. The
function of the atrioventricular valves was intact.
The patient’s medical history revealed no previous
history of chickenpox, tuberculosis, or sexually
transmitted diseases. The woman had no known al-
lergies to medications or vaccines. Written informed
consent was obtained from the patient for the pub-
lication of the depersonalized case report and any
accompanying data. The patient was fully informed
about the purpose of the study, the use of her ano-
nymized medical information, and her right to with-
draw consent at any time without affecting her med-
ical care. All procedures were conducted in accor-
dance with the Declaration of Helsinki and the
relevant institutional ethical standards.
Menstruation started at the age of 13 and lasted
up to five days. It was regular until the age of 49,
with a cycle of approximately 28 days. Reproduc-
tive history: 1st and 2nd pregnancies — medical
abortion, 3rd pregnancy (at the age of 42) — a
healthy girl, who was five years old at the time of
the mother’s diagnosis. Her family history revealed
two maternal aunts affected by BC: one who died
at the age of 50 and the other who survived up to
the age of 80 following surgical treatment per-
formed two decades earlier (Fig. 1). In the patient’s
family, both parents died of stroke at the ages of 80
and 82, and her maternal aunt died at the age of 70.
Her paternal uncle died at the age of 64 from
thrombosis.
The woman worked for over 25 years as a time-
keeper in an office at a mine, where she was ex-
posed to harmful environmental factors, including
poor ventilation and lighting, background indus-
trial noise, vibrations, and dust in the office area.
Although the work was office-based, it was not en-
tirely free from environmental hazards. The main
harmful factors for the patient included visual
strain, immobility, stress, and potentially adverse
microclimate conditions.
The physical examination revealed a satisfactory
general condition, normal body habitus, and ade-
quate nutritional status (weight 70 kg, height 168
cm, BMI 24.8). Skin and visible mucous mem-
branes were unremarkable. The vesicular breath
sounds were auscultated bilaterally in the lungs.
The heart sounds were clear and rhythmic. Blood
pressure was 120/90 mmHg, pulse 69 bpm, and
body temperature 36.6 °C. The patient’s ECOG
performance status was 1. The abdomen was soft
and non-tender on palpation; the liver and spleen
were not palpable. The bowel movements were
physiological and normal. The indicators of com-
plete blood count, blood biochemical analysis, and
urinalysis were within normal limits.
Molecular genetic testing by NGS, performed at
the Invitae Clinical Laboratory (USA) in July 2022,
revealed the heterozygous carrier status for a variant
in the CASR gene within a multiple-gene panel of 93
analyzed genes (including ATM, BRCA1/2, CDH1,
CHEK2, NBN, NF1, PALB2, RAD51C, STK11, TP53,
etc.). The panel content was defined by the labora-
tory according to current clinical knowledge and es-
tablished gene-disease associations. While expanded
panels may detect additional variants, their clinical
relevance and interpretability may be limited. The
selected panel was therefore deemed suitable for the
study objectives. The specific mutation identified
68 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
N. Kitsera , Ya. Shparyk, I. Duda, Yu. Mylyan, N. Kunta
was c.2265G>T in the CASR gene, resulting in a mis-
sense substitution: p.Glu755Asp. No pathogenic
variants were detected in the BRCA1, BRCA2,
CHEK2, and PALB2 genes. The CASR variant (Ta-
ble) identified has not been conclusively associated
with BC and is currently classified as a Variant of
Uncertain Significance (VUS).
Between June 16 and August 18, 2022, four cycles
of neoadjuvant chemotherapy (NACHT) were per-
formed, consisting of endoxan 600 mg/m² IV and
epirubicin 75 mg/m² IV every three weeks. From
September 8 to September 29, 2022, the patient re-
ceived two cycles of paclitaxel at a dose of 175 mg/
m² IV every three weeks. One month later, from Oc-
tober 20 to November 10, 2022, two cycles of
docetaxel at a dose of 80 mg/m² IV every three
weeks were administered. The side effects of chemo-
therapy included nausea (Grade 1) and hair loss
(Grade 3).
After NACHT, the patient underwent a comput-
ed tomography (CT) scan of the chest at the end of
October 2022 (Fig. 2). On preoperative CT in axial
(a), coronal (b), and sagittal (c) reconstructions on
the border of the upper quadrants of the right
breast, approximately at 11—12 o’clock on the con-
ventional dial, a small focus of 11 × 8 × 10 mm of
irregular shape, low-intensity accumulation of con-
trast with fuzzy contours and a homogeneous
structure was visualized. The low degree of contrast
enhancement of the formation was a result of the
therapy (arrow). In the right axillary region, sever-
al lymph nodes measuring 6 × 5 × 6 mm were visib
le (in dynamics, compared with mammography,
they decreased) (thick arrow).
A simple unilateral right-sided mastectomy and
radical axillary lymph node dissection were per-
formed on December 9, 2022. Histological exam-
ination on December 20, 2022, revealed nipple tis-
sue without pathological features and breast tissue
with fibrosis. Ten lymph nodes demonstrated sinus
histiocytosis, consistent with complete pathological
regression (pCR). Diagnosis: right BC, clinical
stage cT3cN1M0 (stage IIIA), pathological stage af-
ter NACHT — ypT0ypN0M0.
A bone scan on November 03, 2023, revealed no
metastasis in the bones.
From November 2022 to December 2023, the pa-
tient received 17 intravenous injections of trastu-
zumab 6 mg/kg every three weeks (the first dose
was 8 mg/kg). Trastuzumab, a targeted therapy, was
prescribed for the treatment of HER2+++ BC to
specifically block tumor growth, enhance treat-
ment effectiveness, reduce the risk of recurrence
after surgery, and improve overall survival.
CT scan performed on April 5, 2024: Findings
indicated a condition after combined treatment
(NACHT and right-sided mastectomy with radical
removal of lymph nodes in the axillary cavity) for
right breast cancer, stage pT3N0M0. No signs of
local recurrence were detected at the time of exam-
ination. Additionally noted were a cyst in the upper
posterior mediastinum (possibly enterogenic),
functional gallbladder disorders, dolichosigma, and
degenerative changes in the spine consistent with
spondylosis. A focus of enostosis was observed in
the body of L3 and in the left lateral masses.
After ten months, the patient’s condition was sa
tisfactory, with laboratory results showing normal
Fig. 1. Family tree of a female BC patient carrying a CASR gene mutation
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 69
A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer
values. A CT scan was performed on February 21,
2025: Findings indicated a condition after combined
treatment (NACHT and right-sided mastectomy,
radical removal of lymph nodes in the axillary cavi-
ty) for right breast cancer, pT3N0M0. Fig. 3 shows
the results of a postoperative CT scan of the chest in
axial (a), coronal (b), and sagittal (c) projections,
where no pathological formations were detected
along the postoperative scar. CT findings: Status af-
ter NACT, right-sided mastectomy, and radical re-
moval of lymph nodes in the right axillary fossa. The
postoperative scar changes in the right axillary area.
No enlarged cervical, supraclavicular, infraclavicular,
or axillary lymph nodes were visible. No signs of lo-
cal recurrence were detected at the time of examina-
tion. Additional findings included functional disor-
ders of the gallbladder, a small liver cyst, a dolicho-
sigmoid, and degenerative changes in the spine
consistent with spondylosis. The focus of enostosis
was observed in the body of L3 and in the left later-
al masses. Compared to the previous CT scan, no
negative dynamics were observed. At the time of the
examination in October 2025, the patient was in re-
mission, her weight was 67 kg, BMI was 23.7.
Discussion
This case report, although demonstrating a poten-
tial association between a rare CASR mutation and
BC, has several important limitations. First, the
identified CASR variant (c.2265G>T, p.lu755Asp)
is classified as a VUS, and to date, there is no direct
evidence of its pathogenicity or functional impact
on the receptor. Second, we were unable to perform
family sequencing to determine whether the muta-
tion was inherited and whether other family mem-
bers, especially the patient’s daughter (due to the
cost of the analysis) or similarly diagnosed relatives
(who were deceased at the time of the proband’s
diagnosis), limited our ability to define the role of
CASR in the familial oncogenetic context.
The identification of a heterozygous CASR
c.2265G>T (p.Glu755Asp) variant in this patient,
currently classified as a VUS, raises intriguing
questions regarding its potential oncological rele-
vance. Although no direct association between this
specific mutation and BC has been previously re-
ported, emerging evidence underscores the patho-
physiological role of CASR in tumor progression
and metastasis, particularly in breast malignancies.
While pathogenic CASR mutations are primari-
ly associated with disorders such as FHH and au-
tosomal dominant hypocalcemia, emerging data
indicate that CASR signaling may play a role in the
development and progression of several cancers,
including BC [11—13]. CASR activation may be a
potent therapeutic target to reduce chemothera-
py-associated diarrhea [14].
In BC models, the overexpression of CASR en-
hances osteolytic metastasis and tumor migration
through the activation of the PTH-related protein
(PTHrP)–Ca²+–CaSR axis, forming a positive feed-
back cycle that promotes bone invasion via PTHrP
secretion [15, 16]. This mechanism aligns with
clinical observations showing higher CASR expres-
sion in HER2+++ carcinomas, similar to the strong
(+++) HER2/neu status in our patient, and associ-
ates with higher Ki‑67 and nodal involvement. At
Key molecular annotation of CASR c.2265G>T (p.Glu755Asp)
Parameter Description Source
Gene CASR (Calcium-Sensing Receptor) https://www.genenames.org
Variant (cDNA) c.2265G>T NGS assay (Invitae)
Protein Change p.Glu755Asp https://www.uniprot.org
Variant Type Missense Sequence analysis
Population Frequency Rare variant Karczewski et al. [8]
https://gnomad.broadinstitute.org
ClinVar Classification Variant of Uncertain Significance (VUS) Landrum et al. [9]
https://www.ncbi.nlm.nih.gov/clinvar
ClinGen Interpretation No validated association with breast cancer https://clinicalgenome.org
ACMG/AMP Classification Variant of Uncertain Significance Richards et al. [10]
Clinical Significance Uncertain; no direct clinical implication Consensus interpretation
70 ISSN 1812-9269. Experimental Oncology 48 (1). 2026
N. Kitsera , Ya. Shparyk, I. Duda, Yu. Mylyan, N. Kunta
the cellular signaling level, CASR stimulates the
Gβγ–PI3K–AKT–mTORC2–Rac pathway, enhanc-
ing cancer cell migration and survival [17]. This
oncogenic signaling may synergize with HER2
pathways in HER2+++ tumors, further amplifying
invasive and metastatic behavior. Furthermore,
CASR activation can stimulate the PI3K/AKT and
MAPK signaling pathways, which are critical for
breast cancer cell survival and invasion [13].
In breast tumors, CASR appears to promote
proliferation and inhibit apoptosis via intracrine
PTHrP mechanisms, thereby enhancing survival
in calcium-rich microenvironments, such as bone
[13]. Given the patient’s HER2+++ status, the
presence of a CASR variant might hypothetically
contribute to tumor aggressiveness or influence
the therapeutic response, particularly in calci-
um-rich environments or in the context of bone
microenvironments.
Importantly, this patient had a positive family
history of BC on the maternal side, with two aunts
affected, although no BRCA1/2 mutations were de-
tected. This observation is compatible with a mul-
tifactorial model of disease, in which genetic pre-
disposition may involve variants outside the classi-
cal high-penetrance genes. Within this framework,
the CASR c.2265G>T (p.Glu755Asp) variant may
be interpreted cautiously as a component of back-
ground genetic variability with potential low-pe
netrance effects rather than an independent patho-
genic alteration. Rare variants of uncertain signifi-
cance could hypothetically influence disease
susceptibility or clinical heterogeneity through in-
teractions with other genetic and environmental
factors. The aggregation of complex disorders ob-
served in the family is consistent with this polyge
nic and multifactorial paradigm.
A mutation in the CASR gene does not protect,
but rather contributes to the development of stroke
damage [18]. Therefore, in the proband’s pedigree,
the mother and her sister died of stroke. It is possi-
ble that they were also carriers of the mutation in
this gene.
Importantly, while studies to date have focused
on CASR expression and signaling, the functional
consequences of rare CASR missense mutations —
Fig. 2. Computed tomography scan of the chest in axial (a), coronal (b), and sagittal (c) reconstructions at the level of
the upper quadrants of the right breast in a woman with breast cancer after neoadjuvant chemotherapy. A small lesion
measuring 11 × 8 × 10 mm with an irregular shape, low-intensity contrast enhancement, indistinct margins, and a ho-
mogeneous internal structure is visualized
Fig. 3. Postoperative computed tomography scan of the chest in axial (a), coronal (b), and sagittal (c) views along the
course of the postoperative scar. No pathological formations were detected. Condition after NACT, right-sided mastec-
tomy, and radical excision of the lymph nodes in the right armpit
ISSN 1812-9269. Experimental Oncology 48 (1). 2026 71
A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer
like p.Glu755Asp — remain unclear. The p.Glu-
755Asp substitution, located in the intracellular
C-terminal region, could plausibly alter \the recep-
tor conformation or downstream coupling, similar
to other clinically significant CASR mutants [19].
Finally, while BRCA1/2 were negative, the identifi-
cation of this novel CASR variant expands the ge-
netic inquiry beyond classical susceptibility genes. It
exemplifies the value of comprehensive sequencing
approaches in uncovering rare variants with un-
clear but potentially actionable implications.
This case highlights the potential role of rare
CASR mutations in BC, particularly among
HER2+++ patients with a familial history but no
mutations in genes with high penetrance, BRCA1/2,
CHEK2, and PALB2. Although the p.Glu755Asp
variant remains a VUS, the biological plausibility
of CASR involvement in BC pathogenesis, through
calcium signaling and metastatic progression, re-
quires further investigation. Functional studies
and the inclusion of CASR in broader BC gene
panels may provide new insights into risk assess-
ment and the development of targeted treat-
ment trategies.
To establish a definitive causal relationship bet
ween CASR mutations and the development of
HER2+++ BC, future multicenter studies with
large patient cohorts, detailed bioinformatic ana
lyses of CASR variants, and investigations of CASR
expression in HER2+++ tumors are necessary.
These efforts will enhance our understanding of
the calcium receptor’s potential role in breast car-
cinogenesis and its value as a biomarker or thera-
peutic target.
Conflict of interest
The authors declare no potential conflicts of inte
rest concerning the research, authorship, and/or
publication of this article.
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Submitted: October 09, 2025
Н. Кіцера 1, Я. Шпарик 1, І. Дуда 1,
Ю. Милян 1, Н. Кунта 3
1 Львівський онкологічний регіональний
лікувально-діагностичний центр, Львів, Україна
2 Івано-Франківський національний медичний
університет, Івано-Франківськ, Україна
3 Львівський національний медичний університет
ім. Данила Галицького, Львів, Україна
ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ
З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ
Гени з високою пенетрантністю, такі як BRCA1, BRCA2, TP53, PALB2, CHEK2 та ATM, добре відомі при спадко-
вому раку грудної залози, на відміну від генів з низькою пенетрантністю, котрі теж можуть відігравати важли-
ву роль у підвищенні ризику захворювання. Ген CASR (Calcium-Sensing Receptor), розташований на хромосомі
3q13.3–q21, кодує рецептор, пов’язаний із G-білком, який регулює гомеостаз кальцію та секрецію паратирео-
їдного гормону. В цьому повідомлені описано клінічний перебіг і генетичні особливості в пацієнтки з раком
грудної залози, у якої виявлено рідкісну мутацію гена CASR та проаналізовано потенційну роль цього гена у
спадковій схильності до розвитку раку грудної залози. Секвенування нового покоління (NGS) виявило гетеро-
зиготний варіант CASR c.2265G>T (p.Glu755Asp), класифікований як варіант невизначеної значущості (VUS).
Патогенних мутацій у BRCA1/2, CHEK2 або PALB2 не виявлено. Пацієнтка отримала неоад’ювантну хіміоте-
рапію, їй проведено правобічну мастектомію та терапію трастузумабом. Вона досягнула повної патологічної
регресії (pCR) без рецидиву впродовж 10 місяців спостереження. Незважаючи на відсутність доведеного пато-
генного значення варіанта CASR p.Glu755Asp, наявні дані свідчать, що надмірна експресія CASR може сприя-
ти прогресуванню HER2-позитивного раку грудної залози через кальцій-залежні сигнальні шляхи (PI3K/AKT,
MAPK). Представлений випадок підкреслює потенційну роль CASR як гена схильності з низькою пенетрант-
ністю та обґрунтовує необхідність подальших функціональних і геномних досліджень для визначення його
клінічного значення.
Ключові слова: рак грудної залози, сімейний анамнез, мутація гена CASR, HER2+++, трастузумаб, Україна.
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| id | oai:ojs2.ex.aqua-time.com.ua:article-620 |
| institution | Experimental Oncology |
| keywords_txt_mv | keywords |
| language | English |
| last_indexed | 2026-06-16T01:00:10Z |
| publishDate | 2026 |
| publisher | PH Akademperiodyka |
| record_format | ojs |
| resource_txt_mv | exp-oncologycomua/fe/d0fe1eaa7f5605760353d8c654400ffe.pdf |
| spelling | oai:ojs2.ex.aqua-time.com.ua:article-6202026-06-15T10:40:08Z A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ Kitsera, N. Shparyk, Ya. Duda, I. Mylyan, Yu. Kunta, N. breast cancer, family history, CASR gene mutation, hER2+++, trastuzumab, Ukraine. Although highly penetrant genes such as BRCA1, BRCA2, TP53, PALB2, CHEK2, and ATM are well known in hereditary breast cancer, genes with low penetrance may also contribute to the disease risk. The CASR (Calcium-Sensing Receptor) gene, located on chromosome 3q13.3–q21, encodes a G-protein-coupled receptor that regulates calcium homeostasis and parathyroid hormone secretion. here we describe the clinical course and genetic findings in a breast cancer patient diagnosed with hER2-positive (hER2/neu +++) and ER/PR-negative infiltrating ductal carcinoma with a rare CASR mutation and explore its potential role in the hereditary breast cancer predisposition. Next-generation sequencing re- vealed a heterozygous CASR variant, c.2265G>t (p.Glu755Asp), classified as a variant of uncertain significance (VUS). No pathogenic mutations were found in BRCA1/2, CHEK2, or PALB2. The patient underwent neoadjuvant chemothera- py, right-sided mastectomy, and trastuzumab therapy, achieving complete pathological regression (pCR) with no recur- rence after ten months of follow-up. Although the CASR p.Glu755Asp variant’s pathogenic role is unproven, emerging evidence links CASR overexpression with hER2-positive breast cancers, promoting tumor progression via calcium- dependent signaling pathways (PI3K/AKt, MAPK). This case highlights the potential role of CASR as a low-penetrance susceptibility gene in breast cancer and supports further functional and genomic studies to clarify its clinical impact. Гени з високою пенетрантністю, такі як BRCA1, BRCA2, TP53, PALB2, CHEK2 та ATM, добре відомі при спадковому раку грудної залози, на відміну від генів з низькою пенетрантністю, котрі теж можуть відігравати важливу роль у підвищенні ризику захворювання. Ген CASR (Calcium-Sensing Receptor), розташований на хромосомі 3q13.3–q21, кодує рецептор, пов’язаний із G-білком, який регулює гомеостаз кальцію та секрецію паратиреоїдного гормону. В цьому повідомлені описано клінічний перебіг і генетичні особливості в пацієнтки з раком грудної залози, у якої виявлено рідкісну мутацію гена CASR та проаналізовано потенційну роль цього гена у спадковій схильності до розвитку раку грудної залози. Секвенування нового покоління (NGS) виявило гетерозиготний варіант CASR c.2265G>t (p.Glu755Asp), класифікований як варіант невизначеної значущості (VUS). Патогенних мутацій у BRCA1/2, CHEK2 або PALB2 не виявлено. Пацієнтка отримала неоад’ювантну хіміотерапію, їй проведено правобічну мастектомію та терапію трастузумабом. Вона досягнула повної патологічної регресії (pCR) без рецидиву впродовж 10 місяців спостереження. Незважаючи на відсутність доведеного патогенного значення варіанта CASR p.Glu755Asp, наявні дані свідчать, що надмірна експресія CASR може сприяти прогресуванню hER2-позитивного раку грудної залози через кальцій-залежні сигнальні шляхи (PI3K/AKt, MAPK). Представлений випадок підкреслює потенційну роль CASR як гена схильності з низькою пенетрантністю та обґрунтовує необхідність подальших функціональних і геномних досліджень для визначення його клінічного значення. PH Akademperiodyka 2026-06-14 Article Article application/pdf https://exp-oncology.com.ua/index.php/Exp/article/view/620 10.15407/exp-oncology.2026.01.066 Experimental Oncology; Vol. 48 No. 1 (2026): Experimental Oncology; 66-72 Експериментальна онкологія; Том 48 № 1 (2026): Експериментальна онкологія; 66-72 2312-8852 1812-9269 10.15407/exp-oncology.2026.01 en https://exp-oncology.com.ua/index.php/Exp/article/view/620/465 Copyright (c) 2026 Experimental Oncology https://creativecommons.org/licenses/by-nc-nd/4.0/ |
| spellingShingle | Kitsera, N. Shparyk, Ya. Duda, I. Mylyan, Yu. Kunta, N. ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ |
| title | ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ |
| title_alt | A Case Report: A Rare Casr Mutation Associated with HER2-Positive Breast Cancer |
| title_full | ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ |
| title_fullStr | ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ |
| title_full_unstemmed | ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ |
| title_short | ВИПАДОК РІДКІСНОЇ МУТАЦІЇ CASR, ПОВ’ЯЗАНОЇ З HER2-ПОЗИТИВНИМ РАКОМ ГРУДНОЇ ЗАЛОЗИ |
| title_sort | випадок рідкісної мутації casr, пов’язаної з her2-позитивним раком грудної залози |
| topic_facet | breast cancer family history CASR gene mutation hER2+++ trastuzumab Ukraine. |
| url | https://exp-oncology.com.ua/index.php/Exp/article/view/620 |
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