Perspective
Breast Cancer and Ovarian Cancer in Monozygotic Twins
Cameselle-Teijeiro JF1-3*, Cortizo LC3, Pons JV1,3, Pérez IF1, Lamas-González MJ1, Faustino SI1, Alonso EF4, Cortizo-Torres ME1,3, Salgado AI3, Costas MS3 and Schmitt FC2
University Hospital of Vigo, Spain
*Corresponding author: Cameselle-Teijeiro JF, Universitary Hospital of Vigo, Clinical Oncology Research Center ADICAM, Travesía de Vigo nº 2, 2º C VIGO 36206 VIGO, Spain
Published: 06 Jun, 2016
Cite this article as: Cameselle-Teijeiro JF, Cortizo LC, Pons
JV, Pérez IF, Lamas-González MJ,
Faustino SI, et al. Breast Cancer and
Ovarian Cancer in Monozygotic Twins.
Clin Oncol. 2016; 1: 1016.
Abstract
We shows the case of three pairs of monocygotic twins in our local area where we carried out our
research: in the first pair of identical twins (case 1), one of them was diagnosed at the age of 43 with
bilateral ovum cancer and the other one with left ovum cancer at the age of 48. In both cases: high
risk cancer, dying of neoplasia dissemination 5 and 6 years after the diagnosis. The genetic study of
BRCA was not carried out. In the second pair of monocygotic twins (case 2), only one of them was
diagnosed with breast cancer at the age of 39, while the other twin presents no cancer after 10 years
of the diagnosis of her identical twin. Although the genetic study BRCA1 and 2 in this family came
out negative, the other pair of twins was diagnosed with bilateral breast cancer: one of them at 39
and 40 years old, and the other at 50 and 58 years old. In 2002, we published the case of a pair of
monocygotic twins (case 3) that were diagnosed with BC, one of them at 55 and 61 (bilateral BC)
and the other at 60 (right BC). The new achievements in genetics, both in the understanding of the
human genome as well as in reducing costs, should lead to a much more regular use of DNA tests to
improve the prevention of breast and hereditary ovum cancer syndromes, through oophorectomy
and/or prophylactic mastectomy. This will also increase the "Preimplantational Genetic Diagnosis"
and will make it more popular through assisted reproductive techniques in families with a high
risk, where the possibility of selecting embryos free of genetic mutation should be offered for its
implantation and gestation.
Keywords: Breast cancer; Ovarian cancer; Monozygotic twins; Chronobiology; Hereditary cancer
Perspective
Breast cancer is a multifactorial disease. Regarding inheritance, we must distinguish three
categories: Esporadic BC, Familial BC and Hereditary BC [1-6]. The first documentation of familial
clustering of breast cancer in modern times was published by Broca, who reported 10 cases of
breast cancer in 4 generations of his wife's family [7]. In the middle of the nineteen nineties it
was demonstrated at molecular level that a substantial number of breast and ovarian cancers has
hereditary monogenic a etiology [8,9]. The Hereditary BC represents at least 10% of breast cancers
and are caused by pathogenic mutations in the considered reference BRCA1 [8] and BRCA2 [9] genes. Based on results of published studies in pairs of monozygotic twins with at least one of them
affected by breast cancer, we can affirm that the lifetime breast cancer risk for a healthy identical
twin, in a non BRCA woman is around 20-30%. Obviously, other non-hereditary risk factors
must exist to explain the discordant phenotype. This highlights that environmental factors play an
important role in breast cancer development.
As sequencing technologies evolve, more susceptible genes have been discovered and BRCA1
and BRCA2 predisposition seems to be only one part of the story. These new findings include rare
germline mutations in other high penetrant genes, the most important of which includes TP53
mutations in Li-Fraumeni syndrome [10], STK11 mutations in Peutz-Jeghers syndrome [11], and PTEN mutations in Cowden syndrome [12].
Theoretically, the comparison between concordance rates for Cancer in monozygotic and
dizygotic twins could give information about the genetic factors in these types of cancer. A large,
new study of identical and fraternal twins in Nordic countries finds that when one twin is diagnosed
with any type of cancer, there is a higher than average risk that the other twin will also develop
cancer. This risk of developing cancer was an estimated 14 percent higher in identical twins if
one twin had cancer and 5 percent higher in fraternal twins if one
twin had cancer — compared to the average cancer risk of all the
people in the study [13]. According to the evidences in monozygotic
twins and considering some families with intense family addition
in Breast Cancer, we can consider that it exists a genetic program
which determines the simultaneity in the time of the beginning of
the tumor; therefore we suggest tackling the chronobiology as a new
clinical variable in the study of Hereditary BC [14].
At the beginning twin studies comparing the disease concordance
rate in identical twin pairs helped us to differentiate the influence of
genetic and environmental factors in the disease development. The
discordance observed in some of these monozygotic twins pairs
confirmed the importance of environmental factors [15]. These studies
are based on the fact that monozygotic twins, those who are formed
from the split of a unique fertilized ovum, have the same genome and
therefore are genetically identical. In theory, the comparison between
percentages of concordance in the BC in monozygotic and dicygotic
twins gives us the information about the genetic factors in this kind
of cancer.
Once we have confirmed the influence of the environmental
factors in the development of breast cancer, we would like to point
out that twin studies provide us with the opportunity to study the
biological clock which predicts the starting date of the carcinogenesis.
There is a coincidence or at least a tendency towards similar ages in
the age of appearance of the breast cancer in monozygotic twins, as
well as in the members of the same family with Hereditary Breast
Cancer Syndrome, that must be studied in depth. In the Table 1 we
show the case of three pairs of monozygotic twins in our local area
where we carried out our research:
In the first pair of identical twins (case 1), one of them was
diagnosed at the age of 43 with bilateral ovum cancer and the other one
with left ovum cancer at the age of 48. In both cases: high risk cancer,
dying of neoplasia dissemination 5 and 6 years after the diagnosis.
The genetic study of BRCA was not carried out. Miesfeldt et al. [16]
reported breast and ovarian cancer syndrome in an identical twin
pair with similar clinical histories and with gen BRCA1 mutation.
Both twins developed histologically similar ovarian cancer in their
mid-fifties. One twin was diagnosed with stage III disease and died
of refractory metastatic disease. The other twin was diagnosed with
stage I disease but ultimately died of recurrent disease. Neither twin
developed breast or colon cancer. Advanced ovarian adenocarcinoma
presented within 3 years in identical twins is reported. The carcinomas
presented at a similar stage and the microscopic appearances showed
strong histological similarities [17].
In the second pair of monozygotic twins (case 2), only one of them
was diagnosed with breast cancer at the age of 39, while the other twin
presents no cancer after 10 years of the diagnosis of her identical twin.
Although the genetic study BRCA1 and 2 in this family came out
negative, the other pair of twins was diagnosed with bilateral breast
cancer: one of them at 39 and 40 years old, and the other at 50 and 58
years old. Sato et al. [18] described a family which involved identical
twin sisters who underwent surgical treatment for a unilateral breast
cancer at the same age of 28. Each, after 13 years, developed cancer in
the opposite breast. In addition yet another sister, the youngest, had
to undergo the same surgical procedure, at the same age her identical
twin sisters had had their first operations. These findings may indicate
the existence of factors which decide the age of the malignancy onset,
in addition to the existence of a predisposing factor for carcinoma in
the genes of breast cancer patients.
In 2002, Cortizo-Torres et al. [14] published the case of a pair of
monozygotic twins (case 3) that were diagnosed with BC, one of them
at 55 and 61 (bilateral BC) and the other at 60 (right BC).
By looking at our table [14] we can reach the same conclusion
that Heizer and Lewison [19] observed in 1964 after reviewing the
medical literature on breast cancer in identical twins: There was a
strong tendency for these tumors to be located in the same breast and
presented at the same time.
Thanks to the advance in the interpretation of the genetic code
maybe we will be able to understand, in the future, how the biological
clock starts the beginning of cancer. Cancer in pairs of identical twins
is a good model for the study of molecular genetics and its interaction
with the environment. The new achievements in genetics, both in the
understanding of the human genome as well as in reducing costs,
should lead to a much more regular use of DNA tests to improve the
prevention of breast and hereditary ovum cancer syndromes, through
oophorectomy and/or prophylactic mastectomy. This will also
increase the "Preimplantational Genetic Diagnosis" and will make it
more popular through assisted reproductive techniques in families
with a high risk [20], where the possibility of selecting embryos free of
genetic mutation should be offered for its implantation and gestation.
Table 1
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