.

Introduction

The most typical form of cancer is breast cancer, which is the second leading cause for death. The
primary explanation for mortality in women aged 45-55 years is this disorder and is the second
leading cause of cancer-induced death. The prevalence of breast cancer is about 1 in 8 women,
much of the time involving complete removal of tissue, chemotherapy, radiotherapy, and hormone
therapy. Breast cancer is a form of tissue cancer that primarily includes milk glands or lobules and
ducts within the inner layer. The first cancer risk factors include age, high levels of hormones, race,
economic class, and dietary iodine deficiency. In one step of this pathogenic mechanism, breast
cancer can be a multi-stage disease in which viruses play a part. Generally, viruses include multiple
forms of cancer. Breast cancer remains the primary cancers, passing at the speed of comprehensive
incidence and death rising every year in women worldwide.

In the last decade, women with stage I and II cancers grew from 41% to 65%, 80% of which are
intrusive cancers, starting with ductal carcinoma and its variations. Present early development
techniques allow for the study of breast malignant growth at an early stage where fruitful therapy is
more possible. Mammography is endorsed by numerous institutions and organisations across the
globe as the best approach to identifying breast cancer at an early stage, especially in women aged
50 years and older.

While multiple treatment choices, including surgery, radiation therapy and chemotherapy, are
currently available, specific treatment strategies rely on factors such as cancer type, hormone
receptor status, metastatic potential, and patient and molecular profile. Chemotherapy is also the
most widely used and prescribed treatment choice for breast cancer, either with the use of a single
compound or multi-drug combination therapy.

Chemotherapy medications, however, have narrow therapeutic indices, which contribute to non-
selective toxic effects on normal tissues, thus raising the risk of infection. Although chemotherapy
and radiotherapy are successful against breast cancer, multiple side effects are correlated with
them, including vasomotor syndrome (occurring in up to 80 % of patients), nausea and vomiting
(75%), postmastectomy enema (30-60%), arthralgia (over 40%), neutropenia, cachexia, weakness,
discomfort, hair loss, hot flushes, and psychological tension.

Risk Factors/Factors of susceptibility of Breast Cancer

An elevated risk for the occurrence of female breast cancer has been associated with age,
reproductive factors, personal or family history of breast disease, genetic pre-disposition and
environmental factors.   average of 1 in 8 women in the U.S develop breast cancer. Proliferative
atypia-free cancers of the breast confer a smaller, greater risk of contracting breast cancer, about
1.5-2 times that of the general population. Atypical hyperplasia, typically occasionally discovered in
screening mammography, for both ductal and lobular, confers a substantially elevated risk. 

The greatest risk is associated with a growing number of first-degree relatives diagnosed with early
years breast cancer (under 50 years of age) and with one, two, three or more first-degree relatives
affected. 
Early menarche is a risk factor for the occurrence of breast cancer in both premenopausal and
postmenopausal people. Breast feeding can delay the return of normal cycles of ovulation and
decrease levels of endogenous sex hormones. An elevated risk of breast cancer has been related to
high levels of serum testosterone [relative risk (RR), 2.86-3.28]. An elevated risk of breast cancer has
also been linked with the later onset of menopause.

Data shows a link between the use of hormone replacement therapy (HRT) and the risk of breast
cancer. Breast cancers due to the use of HRT are typically positive for hormone receptors. The risk of
breast cancer in HRT users is greater in people who do not use HRT. The timing and length of HRT
tend to be significant risk dependent factors. Modifiable risk factors, including heavy alcohol
consumption, obesity and physical inactivity, account for 21% of all deaths worldwide from breast
cancer. Binge drinking has been linked with breast cancer, but not the amount of drinking.
Consumption of alcohol is associated with an elevated risk of the disease at levels as low as 5.0 to
9.9 g per day, equal to 3 to 6 drinks per week.

Postmenopausal women who did not use HRT had elevated breast cancer risk with increasing
weight, body mass index (BMI), and hip circumference. Lean women on HRT are incongruously at an
increased risk of breast cancer. Insulin resistance and hyperinsulinemia have been studied as a risk
factor for the comorbidities associated with obesity including cardiovascular disease and diabetes.
Radiation exposure from various sources including medical treatment and nuclear explosion
increases the risk of female breast cancer and is associated with younger age, particularly in Japan
and Ukraine.

Diagnosis and Treatment Methodologies used

Tests are done to study the cancer cells if cancer is found.

The right care choices of treatment are based on the outcomes of these studies. The tests provide
specifications about:

 How rapidly cancer can spread.

 How possible it is to propagate cancer across the body.

 How well it might work for certain treatments.

 How probable it is for cancer to recur

Now, surgery, radiation therapy (RT), chemotherapy (CT), endocrine (hormone) therapy (ET), and
targeted therapy are the primary methods of breast cancer treatment.

The trending method in the treatment of localised breast cancer is breast conservation procedure.
The procedure is followed by neoadjuvant therapy minimize cancer bulk. Surgery is typically
accompanied by adjuvant treatment to ensure maximum healing and reduce the possibility of
metastases. Radiation can destroy cancer cells that may not be detected after surgery and decrease
the risk of local cancer recurrence. RT is a method in which cancer cells are immediately exposed
and elevated doses of radiation. RT, in combination with CT, shrinks the cancer following surgery.

Side Effects due to treatment

In the United States, 64 % of adults diagnosed with cancer today can hope to be alive in 5 years, with
breast cancer survivors making up the main group of cancer survivors (22 percent ) , followed by
prostate cancer survivors (17 percent) and colorectal cancer survivors (11 percent).The actuarial
survival statistics for early-stage breast cancer in last 10-years, Indian breast cancer patients is 77 %. 
Both chemotherapy and radiotherapy (RT) may very well be linked to the late consequences of
cancer treatment in breast cancer.

Both postoperative radiation therapy (RT) and chemotherapy decrease local recurrence risk and
extend overall survival of breast cancer (BC) patients. However, since the number of women treated
is high and their estimated lifespan is long relative to other patients with other malignant diseases,
questions have been raised about the risk of acute and permanent side effects of breast cancer
survivors. Examples of the broad variety of risks associated to the treatment are heart toxicity,
sexual failure, pneumonitis (RP), arm lymph edoema, neuropathy and skin shifts.

Hot flashes, joint pain, and bone thinning can be caused by hormonal therapy. Hair loss, diarrhoea,
neuropathy, exhaustion, and mouth sores may be caused by chemotherapy. Itching, soreness, and
peeling skin can be caused by radiation therapy. Targeted drugs can cause side effects, including
vomiting, weakness, and diarrhoea, which are similar to chemotherapy.

Many side effects go away very easily, but others can take months to go away entirely, or even
years. These are called late effects. Side effects may also last a lifetime, such as when chemo causes
long-term heart, liver, kidney, or reproductive organ damage. Some chemo forms often have
delayed symptoms, such as a second cancer that may occur several years later. Individuals also get
discouraged on how long their treatment lasts or the side effects they have.

Many cancer patients take up advice on how to continue remaining healthy during the treatment, as
well as and after treatment for cancer. Thinking about the value of exercising, as well as what they
need to do, whether they intend to work or return to work afterwards through recovery.

What is Adjuvant Therapy? Its role in Cancer Treatment

Treatment which is offered along with the first (initial) treatment. Adjuvant therapy is an addition
intended to better accomplish the overall purpose the treatment. Typically, this treatment applies to
surgery, accompanied by chemotherapy or radiotherapy which help minimise the chance of
recurrent cancer (coming back). "Adjuvans" in Latin means to support and, in particular, to help
accomplish a goal. Chemotherapy, radiation, hormone treatment, targeted therapy, or biological
therapy can be used in adjuvant therapy.

A comprehension of the proper use of adjuvant treatment in case of breast cancer is especially
important because, breast cancer is the most prevalent cancer diagnosed in western women, except
non-melanomatous skin cancers. Breast cancer prevalence grows with age, and as the population
ages, primary care doctors can expect to see more patients with breast cancer. Any of these women
may have an early-stage condition where adjuvant treatment is expected to be taken into account.
Finally, it would be helpful for primary care clinicians to consider the decision-making process, and
how risks are measured, what advantages are anticipated from treatment, and how to incorporate
other health considerations in order to make an individualised decision on which Adjuvant therapy
can be used for the individuals on basis of their conditions.

Different side effects of cancer therapy are addressed in this study, along with proven beneficial
adjuvant treatments for the same therapy.
1. EXHAUSTION  

Feeling overtired, with low energy and a strong desire to sleep that interferes
with normal daily activities. It’s a term that is used to describe an overall sense
of exhaustion or loss of energy. It isn't the same as getting tired or sleepy. You
have no motivation and no energy because you're sleepy. It can be a sign of
fatigue to be sleepy, but it is not the same thing There are many potential
causes of fatigue. They can be divided into three general categories:
 lifestyle factors
 physical health conditions
 mental health issues(Healthline).
Up to 45% of the U.S. population has reported experiencing fatigue, which
greatly reduces overall quality of life (Ricci, Chee, Lorandeau, & Berger, 2007).
Chronic fatigue that is unresponsive to rest may be a sign of underlying
pathology (Jorgensen, 2008) or chronic illness (Ricci et al., 2007). Much of the
research on fatigue has been conducted in cancer patients, but fatigue is also
common in persons with heart failure (HF), multiple sclerosis (MS), chronic
kidney disease (CKD), rheumatoid arthritis (RA), and chronic obstructive
pulmonary disease (COPD; Junghaenel, Christodoulou, Lai, & Stone, 2011). 
Despite the prevalence of fatigue and its negative impact on the human
experience, research exploring mechanisms of fatigue in different disease
states is limited.

PMC full Biol Res Nurs. 2018 Jul; 20(4): 410–421.

text:
Published online 2018 Mar 14. doi: 10.1177/1099800418764326
Copyright/LicenseRequest permission to reuse
Figure 1.
The underlying biological modifications (inflammation, activation of the
autonomic nervous system, and hypothalamic-pituitary-adrenal axis
dysregulation) that seem to be consistent with fatigue are associated with
chronic diseases. Patient attributes and changeable factors may affect these
biological changes. Cognitive behavioural conditions can influence the
sequence of biological processes outlined in this figure and hinder physical
function, movement, and energy control, and can also affect levels of fatigue.
(Biol Res Nurs. 2018 Jul; 20(4): 410–421.)Cancer researchers have led the way
in identifying and investigating the underlying fatigue mechanisms.
One of the most frequent and distressing side effects of cancer and its
treatment fatigue. Exhaustion may be increased prior to start of treatment and
usually increases during treatment for cancer, including radiation therapy,
chemotherapy, hormone therapy, and/or biologic therapy. The average
incidence of exhaustion during treatment ranges between 25% and 99%, based
on the patient group, level of treatment obtained and form of assessment. In
most studies, 30% to 60 % of patients experience mild to extreme fatigue
during care, which can lead to discontinuation of treatment in some cases. (
Bower J. E. (2014). Cancer-related fatigue--mechanisms, risk factors, and
treatments. Nature reviews. Clinical oncology, 11(10), 597–609.
https://doi.org/10.1038/nrclinonc.2014.127)
Interest in the underlying biological pathways and genetic mechanisms of
fatigue is mounting. Previous literature reviews have reported on potential
biological pathways or etiologies of cancer-related fatigue (Bower, 2014; Ryan
et al., 2007; Saligan et al., 2015). The causes of cancer-related fatigue have
been identified by researchers as inflammation, hypothalamic-pituitary-
adrenal (HPA) axis dysregulation, and/or autonomic nervous system activation
(Bower, 2014; Ryan et al., 2007; Saligan et al., 2015).
Cancer and its treatment have been associated with increases in plasma
cytokines [26]. The mechanisms, however, are not fully understood. Research
has demonstrated that the tumor micro-environment contains pro-
inflammatory cytokines. [33]. For various cancer diagnoses, elevated levels of
circulating cytokines and their receptors (most commonly IL-6) have been
observed at initial diagnosis and after diagnosis of metastasis. These cytokines
can contribute to anemia, cachexia, anorexia, fever, infection and depression,
all of which can contribute to fatigue [34].
Another reason is low levels of cortisol that are associated with fatigue and
may result from the direct suppression of the HPA axis by cancer treatment or
changes in 5-HT that result in decreased stimulation of 5-HT 1A receptors that
signals the release of CRH [43].
Coriolus versicolor (Yunzhi) - also known as Trametes versicolor is a popular
component in TCM mushroom preparations. Several clinical trials with patients
receiving chemotherapy or radiotherapy have found that encapsulated Yunzhi
preparations significantly improve appetite, alleviate weakness, anorexia,
vomiting, dryness of the throat, and spontaneous or night sweats and pain,
increase weight, stabilize white blood cell counts, NK cells, IL-2 levels, and
CD4/CD8 ratio, and demonstrate a 9% absolute reduction in 5-year mortality
rate.

Figure 1. Morphological features of Coriolus versicolor. The various

morphological features of the fungus grown in the UK are shown. While the
upper surface shows concentric zones of colours (red, yellow, green, blue,
brown, black, and white), the picture in the lower-right shows the
polyporous nature of the underside portion of the
 fungus. (https://www.first-nature.com/fungi/trametes-
versicolor.php#distribution).

1. [S. Frei-Kleiner, W. Schaffner, V. W. Rahlfs, C. Bodmer, and M. Birkhäuser, “Cimicifuga

racemosa dried ethanolic extract in menopausal disorders: a double-blind placebo-controlled
clinical trial,” Maturitas, vol. 51, no. 4, pp. 397–404, 2005.View at: Publisher Site | Google
Scholar

2. K. M. Newton, S. D. Reed, A. Z. LaCroix, L. C. Grothaus, K. Ehrlich, and J. Guiltinan,

“Treatment of vasomotor symptoms of menopause with black cohosh, multibotanicals, soy,
hormone therapy, or placebo: a randomized trial,” Annals of Internal Medicine, vol. 145, no.
12, pp. 869–879, 2006.View at: Google Scholar

3. M. D. J. Molla, J. J. Hidalgo-Mora, and M. G. Soteras, “Phytotherapy as alternative to

hormone replacement therapy,” Frontiers in Bioscience, vol. 3, pp. 191–204, 2011.View
at: Google Scholar]

The vitality status findings were consistent with the quality of life using the SF-
36 Health Survey questionnaire: participants experienced less fatigue (P <
0.001), better quality of sleep (P < 0.001), better appetite (P < 0.001), more
regular bowel movements (P < 0.001) and more stable emotion (P < 0.001).
(Wong, L. Y., Wong, C. K., Leung, P. C., & Lam, W. K. (2010). The efficacy of herbal therapy on
quality of life in patients with breast cancer: self-control clinical trial. Patient preference and
adherence, 4, 223–229. https://doi.org/10.2147/ppa.s10961)

Fatigue usually increases in the year following completion of therapy, while fatigue tends to persist
in a large minority of patients for months or years following effective treatment. Long-term cancer
survivors' research show that about one-quarter to one-third report chronic exhaustion following
cancer diagnosis for up to 10 years. Fatigue has a detrimental effect on work, social interactions,
mood and everyday tasks and induces substantial deterioration before and after treatment of the
overall quality of life. Fatigue may also indicate a shorter survival rate.

The hematopoietic system is also smothered by cytotoxic chemotherapy, undermining the healthy
system and limiting the dosages of drugs that the patient can tolerate. In this case, a few drugs, such
as cisplatin-methotrexate fluorouracil, fluorouracil-epirubicin-cyclophosphamide, and FEC-
tamoxifen, have been used in tandem, as adjuvants, to improve viability and alleviate symptoms. A
2
combination chemotherapy including cisplatin, 25 mg/m   on Days 1,8;
methotrexate, 30 mg/m 2 on Day 1; and 5-fluorouracil, 600 mg/m 2 on Day 1
has been evaluated in 28 previously untreated and 10 pretreated patients with
advanced ovarian cancer after debulking surgery when feasible. The
pathological response rates (complete + partial responses) were 69.2 and 50%
in untreated and pretreated patients, respectively. Overall 24-month survival
and progression-free survival (PFS) are 19.2 and 10.9%, respectively. A
significant difference in survival and PFS is evident between patients with less
and more than 2 cm residual disease and between responders (CR + PR) versus
nonresponders. No renal toxicity was induced and no cycles had to be delayed
because of hemathologic toxicity. P.F. Conte, M.R. Sertoli, M. Bruzzone, A.
Rubagotti, R. Rosso, G. Bentivoglio, A. Conio, G. Pescetto,
Cisplatin, methotrexate, and 5-fluorouracil combination chemotherapy for
advanced ovarian cancer,
Gynecologic Oncology,
Volume 20, Issue 3,
1985,
Pages 290-297,
ISSN 0090-8258,
https://doi.org/10.1016/0090-8258(85)90210-0.
(http://www.sciencedirect.com/science/article/pii/0090825885902100)
induced and no cycles had to be delayed because of hemathologic toxicity.
It is apparent that fatigue is related to multiple physical as well as
psychological symptoms. More specifically, study has found that fatigue is
certainly related to pain, sleeping difficulties, and depression. It is not
uncertain if these variables are connected.
What majorly effects in finding out ways to cure such kind of exhaustion, is the
difficulty to differentiate between cancer-related fatigue and ordinary fatigue,
since anyone feels exhaustion on a daily basis. A potential alternative to the
existing dilemma would be to evaluate cancer patients as safe subjects, too.
The bulk of research used in the latest literature review have not included
control groups. Its subjectivity is another challenge in assessing fatigue. It may
also be less disturbing to a person who statistically experiences a high degree
of fatigue than someone who experiences less fatigue.
In an entirely different way, everybody copes with fatigue, and this difference
in coping with fatigue has barely been studied. In comparison, most studies
struggle to discern whether everyday life was impaired by the fatigue
encountered. That breast cancer may be a leading form of cancer in women
who are identified with fatigue as having an excellent influence on the quality
of life suggests that more study is needed. It is expected that ongoing research
will tell us more about fatigue and thus the associated factors and will provide
more information on potential therapies for this complex problem.
2. CHEMOTHERAPY INDUCED TOXICITY

A normal and undesirable outcome of treatment that may arise even at regular doses is
chemotherapy toxicity. Chemotherapy works by damaging cancer cells; however, normal cells are
also vulnerable to injury, and chemotherapy toxicity ensues as this happens. Such toxicities also
require emergency treatment. Timely identification and proper control of the toxicity of
chemotherapy is crucial.

Cytotoxic chemotherapy agents usually interfere with RNA and DNA synthesis
or cell division and, therefore, affect cell growth by various mechanisms of
action. Some of the most commonly used drugs include classic agents such as
cyclophosphamide (an alkylating agent), cisplatin (a DNA intercalating agent), fl
uorouracil (5-FU; an antimetabolite), doxorubicin (an anthracycline), vincristine
(a mitotic spindle inhibitor), and bleomycin. Some of the more recently
developed cytotoxic agents include gemcitabine (another antimetabolite),
oxaliplatin (a cisplatin analog), paclitaxel and docetaxel (the “taxanes,” which
are mitotic spindle poisons), and irinotecan (a topoisomerase inhibitor)
. Drugs that interfere with nucleic acid synthesis and cell division have the
greatest effect on rapidly dividing cells. Therefore, these drugs will also affect
the rapidly dividing cells of the intestine and bone marrow, leading to common
and sometimes dose-limiting gastrointestinal toxicity and myelosuppression.
Nearly any organ can be affected, however, depending on the drug. Peripheral
nerves (e.g., vinca alkaloids, cisplatin, taxanes), lungs (eg, bleomycin and
gemcitabine), kidneys (eg, cisplatin), heart (eg, anthracyclines), and central
nervous system (e.g., high-dose methotrexate, 5-FU) are only a few examples
( Table 3 ).
Now, 5-FU and irinotecan are two chemotherapeutic agents widely used for various cancer
treatments. 5-FU exerts its anticancer effects through inhibition of thymidylate
synthase (TS) and incorporation of its metabolites into RNA and DNA.
1 From the Departments of Radiology (J.M.T., L.H.S., M.J.G., M.S.G., H.H.) and Medicine (G.J.B.),
Memorial SloanKettering Cancer Center, 1275 York Ave, Room C-278, New York, NY 10065. Received
November 16, 2009; revision requested January 13, 2010; revision received March 2; accepted
March 9; fi nal version accepted March 13; fi nal review by H.H. August 27. Address correspondence
to J.M.T. (e-mail: torrisij@mskcc.org ). q RSNA, 2011

In various human cancer cell lines, SW-480, HCT-116 and HT-29, the synergistic tumoricidal effects of
ginseng on 5-FU and irinotecan were examined. It was found that the ginseng extract greatly
Baek et al. have
prevented the growth of cancer cells in a concentration-dependent manner.
found ginsenosides Rh4 and Rk3, the active principles of Sun ginseng (SG), to
significantly reduce the cisplatin-induced nephrotoxicity in LLC-PK1 cells in a
dose-dependent manner. The mechanisms of function and structure-activity
relationships with other ginsenosides remain to be investigated [S. H. Baek, X.
L. Piao, U. J. Lee, H. Y. Kim, and J. H. Park, “Reduction of cisplatin-induced nephrotoxicity
by ginsenosides isolated from processed ginseng in cultured renal tubular cells,” Biological
and Pharmaceutical Bulletin, vol. 29, no. 10, pp. 2051–2055, 2006.].
Ginsenoside Rd may also ameliorate cisplatin-induced renal injury, a process in
which apoptosis may play a central role [T. Yokozawa and E. Dong, “Role of
ginsenoside-Rd in cisplatin-induced renal injury: special reference to DNA
fragmentation,” Nephron, vol. 89, no. 4, pp. 433–438, 2001].
Clinical trials using a natural dietary supplement consisting of a mixture of
Coriolus versicolor, Ganoderma lucidum, and Phellinus linteus medicinal
mushrooms and Scutellaria barbata, Astragalus membranous, and Curcuma
longa medicinal herbs indicated that the formula could relieve liver, spleen,
kidney, lung, and heart tissue chemotherapy-induced toxicity. The mechanism
of action of this mushroom-herbal mixture in inhibiting proliferation and
reducing the invasive activity of the highly metastatic human cancer cell line,
MDA-MB-231, by inhibiting the expression of cyclin A1 and by downregulating
CXCR4 was also elucidated in in vitro tests.
By way of pharmacodynamic and pharmacokinetic herb-tranquilize
partnerships, co-organization of natural medications and physician-
recommended medications can initiate negative effects. Then again, through
way of synergistic exercises, herbs and their metabolites may even maximise
the impact of chemotherapy specialists.
3. HOT FLASHES

A hot flash is a sudden warm feeling over your face, neck, and chest that may cause you to sweat
and your face to turn red. Sweating is your body's way of lowering body temperature by causing
heat loss through your skin. Hot flashes combined with sweats that happen while sleeping are often
called night sweats or hot flushes. Hot flashes and night sweats are common in patients receiving
cancer treatment. Some people continue to have hot flashes and night sweats after cancer
treatment.

Hot flashes are triggered by small elevations in core body temperature (Tc)
acting within a greatly reduced thermoneutral zone, i.e., the Tc region
between the upper (sweating) and lower (shivering) thresholds. This is due in
part, but not entirely, to estrogen depletion at menopause. Elevated central
sympathetic activation, mediated through α2-adrenergic receptors, is one
factor responsible for narrowing of the thermoneutral zone.
The use of an aromatase inhibitor in the treatment protocol for hormone-positive cancers in
postmenopausal women is recommended by nearly all national and international guidelines.
However, commonly reported side effects include hot sweats for both pre- and postmenopausal
women.

Aromatase inhibitors work by inhibiting the action of the enzyme aromatase,

which converts androgens into estrogens by a process called aromatization. As
breast tissue is stimulated by estrogens, decreasing their production is a way of
suppressing recurrence of the breast tumor tissue.
When hormone levels decrease, the reaction is triggered. This same alteration
affects the hypothalamus, the portion of the brain that governs the
temperature of the body and other functions, allowing the signal to be misread
as a warning that the body is too hot. Epinephrine, the message transmitter of
the nervous system, transmits the message across the body immediately. Hot
flashes are the body's effort to rapidly get out of the heat. In an effort to cool
the body down, the heart begins to beat faster, blood vessels in the skin dilate
to expel heat, and the skin continues to sweat.
In Traditional Chinese Medicine (TCM), C.Racemose extract, also known as the black cohosh extract
(BCE) is known to minimise hot flashes and to have low toxicity in menopausal women. This
argument has been backed up by many clinical trials.

Although the mechanism by which BCE relieves symptoms is unknown, several

hypotheses have been proposed: it acts 1) as a selective estrogen receptor
modulator, 2) through serotonergic pathways, 3) as an antioxidant, or 4) on
inflammatory pathways.
A 2012 Cochrane review evaluated 16 randomized clinical trials on the
effectiveness of black cohosh in reducing menopausal symptoms, including hot
flushes, night sweats, vaginal dryness, and combinations of symptoms
measured by validated rating scales [5]. (The two trials discussed above were
included in this Cochrane review.) The 16 included trials randomized a total of
2,027 women (mean age 50.5 to 56.4 years), and their samples ranged from 23
to 351 participants. Study durations were 8 to 54 weeks, with a mean duration
of 22.8 weeks. Participants received a daily dose of various formulations of 8 to
160 mg/day black cohosh extract, with a median dose of 40 mg/day. In some
cases, the authors of the original study reports indicated that the extract they
used came from the root/rhizome, they had extracted the product using
isopropyl alcohol or ethanol, and/or they had standardized the extract to
contain a specific amount of triterpene glycosides. The studies were highly
heterogeneous with respect to such factors as design, duration, type and
amount of black cohosh used, and main findings. The review’s authors
concluded that there was “insufficient evidence” from these trials “to either
support or oppose the use of black cohosh to reduce hot flashes.” Leach, M. J.,
& Moore, V. (2012). Black cohosh (Cimicifuga spp.) for menopausal symptoms.
The Cochrane database of systematic reviews, 2012(9), CD007244.
https://doi.org/10.1002/14651858.CD007244.pub2
In addition, the high antitumor activity of C.Racemosa was seen in in vitro experiments using MCF7
cells. Extracts of Racemosa and their participation in apoptosis induction.

In patients with hot flashes, pilot tests in acupuncture and randomised controlled trials contrasting
real acupuncture and sham (placebo) therapy have been performed and the findings are mixed. In
breast cancer patients with hot flashes, a study of several trials together found that acupuncture has
mild to no effects. In comparison, a randomised controlled study that was not included in the
analysis found that there were less hot flashes in women with breast cancer that were given
acupuncture. Another randomised controlled trial found that there was a drop in hot flash effects
among breast cancer patients who were given electroacupuncture.
Wang XP, Zhang DJ, Wei XD, Wang JP, Zhang DZ. Acupuncture for the relief of hot flashes in breast cancer
patients: A systematic review and meta-analysis of randomized controlled trials and observational studies. J Can
Res Ther 2018;14, Suppl S3:600-8

It may be speculated that during an incident of hot flashes there is a high

neuronal activity in the hypothalamus and that acupuncture may reduce this
activity, perhaps mediated by increased β-endorphin release and decreased
noradrenalin activity. The effect of acupuncture on hot flashes in women and
men is likely to be multifactorial, and it is difficult to achieve placebo-
controlled trials as there are so many components to be controlled for. In the
acupuncture and hot flash trials, attempts have been made to monitor the
needling elements, but little variation between treatment groups is seen in
most cases, although improvements within the group are apparent.
https://doi.org/10.1155/2012/579321

Hot flashes, however, are often likely to lead to impaired compliance with hormone-suppressive
therapies. Family clinicians, oncologists, and nurses will play an important part in both the diagnosis
of hot flashes and the analysis and application of treatment choices to the needs of particular
patients.

4. ORAL ULCERS

One or more painful sores on inner lips, gums, tongue, roof of the mouth or
throat that may interfere with eating, such as a
(https://support.google.com/websearch/answer/2364942?
p=medical_conditions&hl=en-IN&visit_id=637449683311558641-
326956795&rd=1) (apollo hosp) .Mouth ulcers caused by treatment with chemotherapy
typically occur a few days after the start of treatment and go away within two to three weeks after
stopping chemotherapy. After chemotherapy treatment concludes, the mouth sores usually reach
their height during the seventh day.
Integration of molecular pain modeling with current pathobiology for oral mucosal injury associated
with cancer treatment.  © International & American Associations for Dental Research. Reprinted by
Permission of SAGE Publications.

Neurotrophic factors such as NGF are secreted by neurons, inflammatory cells,

and cancer cells, in turn, mediating pain by the binding of these factors to
receptors on peptidergic C fibers 40. Peripheral release from peptidergic C fibers
produces the neurogenic inflammation that characterizes the complex pain
response involved with oral mucositis 4
In patients receiving chemotherapy for solid tumors or lymphoma, the rate of infection during cycles
with mucositis was more than twice that during cycles without mucositis and was directly
proportional to the severity of mucositis 3. Infection-related deaths were also more common during
cycles with both oral and GI mucositis. In addition, the average duration of hospitalization was
significantly longer during chemotherapy cycles with mucositis. Importantly, a reduction in the next
dose of chemotherapy was twice as common after cycles with mucositis than after cycles without
mucositis 3. Thus, mucositis can be a dose-limiting toxicity of cancer chemotherapy with direct
effects on patient survival.
Oral ulcerative mucositis, also , limits the nutritional intake of cancer patients. One clinical study
demonstrated the effects of R. algida in alleviation of the occurrence of oral ulcers after four cycles
of chemotherapy using 5-fluorouracil, epirubicin and cyclophosphamide, and postmasectomy.

The constituents of Rhodiola algida were analyzed by RP-HPLC. Lymphocytes

isolated from 462 healthy subjects were treated with 100 ug/ml Rhodiola
algida for 48 h. The activity of the cells was measured by cell proliferation
reagent and ATP assay. The level of various cytokines and mRNA content of
lymphocytes were determined. Rhodiola algida demonstrated no toxicity in
animals, which had been orally fed with 1 mg/ml Rhodiola algida for 30 days.
130 breast cancer patients from Huaxi Hospital of Sichuan University were
recruited between 2006 and 2007. The optimal concentration of Rhodiola
algida favored the proliferation of lymphocytes. The levels of IL-2, IL-4,
granulocyte-macrophage colony-stimulating factor and the mRNA content of
these cytokines were also enhanced. White blood cell (WBC) levels returned to
normal range in both groups 1 week after every cycle of chemotherapy. WBC
count increased faster in patients using Rhodiola algida; they presented with
smaller and fewer oral ulcers. There were no liver or renal complications
observed in any patients. (https://pubmed.ncbi.nlm.nih.gov/20374035/ )
There were fewer and smaller oral ulcers in the patients and no liver or kidney abnormalities were
found in any of the patients included in the study. So, R. Algida has the ability to be used to relieve
the incidence of oral ulcers at the same time as chemotherapy.

Increase in immunity of patients who are receiving chemotherapy, post

mastectomy and decreases the quantity of oral ulcers. Thus, Rhodiola algida
has the potential to be used concurrently with chemotherapy to alleviate the
occurrence of oral ulcers.
5. MAJOR DEPRESSIVE DISORDER

Serious depressive disorder (MDD) is a disease that is highly complex and heterogeneous. Patients
with MDD have been found to have elevated amounts of pro-inflammatory cytokines, elevated
oxidative stress, impaired gastrointestinal ( GI) activity, and reduced micronutrient and omega -3
fatty acid status. Emerging literatures indicates that dietary effects on MDD are currently
underestimated. In MDD, small intestinal bacterial overgrowth (SIBO) is likely to lead to the minimal
absorption of nutrients. It is understood that stress, a major factor in MDD, alters GI microflora,
reducing lactobacilli and Bifidobacterium levels. Research indicates that, even in the absence of an
immune response, bacteria in the GI tract can associate with the central nervous system. There
has been no consistent identification of an exact mechanism relating the
particular properties of cancer biology to the onset of depression. Here, three
of the key hypotheses that have been suggested are reviewed: the function of
inflammatory mediators, an overactive HPA axis, and neurotransmitter
glutamate excess concentrations. 10.3389/fpsyt.2018.00299
Ginseng is one of the most well-known herbal medicines and is used to enhance fitness, vitality, and
durability proactively in TCM. Ginseng is listed internationally as the fourth top-selling herbal drug.
Ginseng has been used in pharmacopoeias in recent years in Germany, Austria, the United Kingdom,
and the United States. Ginseng has been used in adjuvant breast cancer therapy to preserve natural
vitality, enhance physical and psychomotor performance, and strengthen mood and general health.

Ginsenoside Rb1 and compound K were active ingredients that dose-

dependently prevented the prolongation of immobility time induced by
ovariectomy. Co-administration of ritanserin, a 5-HT 2A-receptor antagonist,
antagonized the effect of ginsenoside Rb1. Yamada, N., Araki, H. & Yoshimura, H.
Identification of antidepressant-like ingredients in ginseng root (Panax ginseng C.A. Meyer)
using a menopausal depressive-like state in female mice: participation of 5-
HT2A receptors. Psychopharmacology 216, 589–599 (2011). https://doi.org/10.1007/s00213-
011-2252-1 In vitro tests and in vivo animal studies have confirmed that ginsenosides have a
number of beneficial effects, including immunomodulatory, anti-stress, antifatigue, and
anticarcinogenic effects, as a group of bioactive compounds found in ginseng.

It has also been seen that probiotics have the ability to lower inflammatory systemic cytokines,
minimise oxidative stress, boost nutritional status, and correct SIBO. Ultimately, the impact of
probiotics on systemic inflammatory cytokines and oxidative stress could lead to increased
neurotrophic factor (BDNF) derived from the brain.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6971226/table/T1/?
report=objectonly (Table)
The current research reveals the importance of growth mixture modelling for analysing depressed
symptomatology over time in people with a cancer diagnosis, despite its limitations. Results with
respect to psychosocial features, which were investigated in previous reports, in cancer-related
trajectories in depressive symptoms, have still been obtained to certain degree. It is motivated by
prospective studies, into pathways at risk of prolonged depressive symptomatology in women
seeking breast cancer care, as well as attempts to develop the right adjuvant treatments in this
patient demographic to resolve the problem of depression.

6. NEUTROPENIA

Chemotherapy is one of the approved therapies for breast cancer, and can require single or multi-
drug combination therapy. In terms of non-selective toxic effects on normal tissues, chemotherapy
medications have very small clinical indices, with neutropenia being the most commonly observed
adverse reaction, raising the risk of infections. Pharmacological treatments that mitigate or avoid
these harmful effects may have a huge impact on the treatment of cancer.

By damaging the DNA of malignant cells, chemotherapy is able to produce

killer malignant cells. Many chemotherapy agents cause bone marrow
suppression resulting in neutropenia, which leads to an increased risk of
infection.h
An overview of granulopoiesis. As with all blood cells, neutrophils begin as
hematopoietic stem cells (HSCs, orange circle) in the bone marrow (pale yellow
background), where they develop. HSCs are capable of self‐renewal and are
subject to cell death (dashed arrows). HSCs may also differentiate into one of
the blood cell lines, including the neutrophils (purple circles). After
commitment to the neutrophil lineage, cells undergo a period of proliferative
expansion at the end of which they no longer divide. Postmitotic neutrophils
then mature, growing in size and gaining receptors. At the end of the
maturation process, cells are then stored in the bone marrow reservoir from
which they egress to reach the circulation (pale red background) before
removal (by margination or death). G‐CSF acts to modulate the rate of exit
from the marrow reservoir, increase the rates of maturation and proliferation,
and to modulate the rate of differentiation into the neutrophil lineage (G‐CSF
actions represented by blue vertical arrows).
Herbal remedies are also used in traditional medicine frameworks to combat these cancer-related
symptoms and the side effects of cancer therapy. Herbal formulas used in TCM include herbal
compound mixtures composed of decoctions, tea, injections, or capsules that are suspected to have
anticancer compounds which are used to boost potency and/or minimise drug-induced neutropenia
alone or as adjuvants to current chemotherapy regimens.

https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6281965/table/T2/?
report=objectonly (Table)
In mouse breast cancer models, the use of LSC101 alongside doxorubicin resulted in slightly higher
neutrophil, splenic erythrocyte, and leukocyte numbers. Along with traditional chemotherapy
regimens, the use of LCS101 saved patients from mild to severe chemotherapy-induced anaemia and
neutropenia, demonstrating its use in reducing patient haematological toxicity.(
https://europepmc.org/article/pmc/pmc3694462#B73)

In women diagnosed with Invasive Ductal Carcinoma-Stage II, Uncaria tomentosa, used at a dosage
of 300 mg dry extract per day, is successful in healing from chemotherapy-induced neutropenia. It
can also restore cellular DNA. Thus, adjuvant treatment is safe and effective in reducing adverse
chemotherapy effects. ( https://www.hindawi.com/journals/ecam/2012/892182/tab3/ )

7. GAIN IN WEIGHT

A typical side effect observed in women receiving breast cancer chemotherapy is weight gain. A
direct impact of chemotherapy on metabolism has been suggested as one of the potential causes.

Although obesity or its effects do not inherently result in weight gain after
diagnosis, any effect on the prognosis of breast cancer and overall health,
patient self-image, or quality of life (QoL) will be an undesirable outcome.
These findings may be interrelated: weight gain may impact other medical
conditions that may affect overall survival, such as diabetes, heart disease,
hypertension and hypercholesterolemia. In the Women's Healthy Eating and
Living (WHEL) study, for instance, Erickson et al[6] found connections between
weight change and the risk of developing diabetes in breast cancer patients.
Perhaps most worrisome, patients seldom return to pre-diagnosis weight[7,8],
which could be correlated with well-described body image issues (in 70
percent of women under age 50 in one study[9]).
(https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4127600/ )
Chemotherapy and radiation cause excess fluid, or edema, to hold on to the body . It
is a
vascular reaction that causes an increased ability for fluid in the cells
to "leak" into the layers of the skin, resulting in swelling. This happens
much less often than hives alone.This induces persons, mostly because of exhaustion,
to limit physical exercise. Along with, nausea, which is gradually increased intake, extreme food
cravings were caused. A decline in the patients' metabolism rate is also seen. Menopause caused,
which reduces metabolism in some women. Steroid drugs also boost the appetite. A rise in adipose
tissue, which may increase the size of the belly of an individual and cause fullness in the neck or
chest.

In cancer patients, the "dose" of physical exercise needed to counteract the deleterious impact of
diagnosis and treatment on weight and adiposity is not clearly established, but data from the general
community shows that it is not negligible.

https://www.ncbi.nlm.nih.gov/books/NBK221839/table/ttt00020/?report=objectonly (Table)

Several myokines are released only during exercise,

and some researchers have proposed that these
exercise-dependent myokines contribute to the
myriad beneficial effects of physical activity for all
individuals (https://www.the-
scientist.com/features/regular-exercise-helps-
patients-combat-cancer-67317)
A meta-analysis of body structure aerobics in patients with cancer and conducted ten trials of
women's fitness strategies at the end of adjuvant therapy. During a total of three sessions per week,
30-40 minutes each of mild exercise.
https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6457768/figure/CD005001-fig-0005/ (table)

The research groups participated and were observed to have reduced body fat level, without major
increases in weight or lean body mass. An analysis of twelve resistance or resistance studies plus
aerobic exercise was conducted. The experiments had different endpoints: one study reported a
decline in WHR, but no substantial improvement existed for those calculating weight, BMI, or fat
mass.

During a narrative analysis, it was identified the impact of physical exercise not only on weight gain,
but also on other treatment side effects, including fatigue, depression, and QoL. Exercise has
additional mood and QoL effects, irrespective of weight loss, and can be promoted right in the
middle of adjuvant therapy after recovery from surgery. Intervention experiments may aim to better
elucidate the importance of physical exercise to the prognosis of cancer.

In summary, relative to overweight and obese responders, cancer patients with a more average BMI
are more likely to perceive post-treatment weight. This is also in contrast to midlife women in the
general population, who are said to add weight with a higher BMI. With greater involvement in daily
physical activity, the load gain and rise in waist circumference encountered over time within the
general population may also be prevented; also, research shows that exercising is a challenge to
reduce weight gain in women following a carcinoma diagnosis.

CONCLUSION

Botanicals have thus been the primary source of treatment for cancer patients in many conventional
medicine schemes and have also been used clinically. Studies have stated that cancer patients
frequently use botanicals to manage the symptoms associated with cancer, to reduce the side
effects of chemotherapy, and probably to improve the effectiveness of chemotherapy agents.

The capacity of botanicals for chemotherapy was upheld by the cycle of disease cells and apoptotic
expectations. In addition, the use of PC-based docking models, botanicals and chemotherapeutic
operators can require distinctive local controls, providing further evidence of their synergistic
practises. Botanicals can also be used to decrease chemotherapy-initiated queasiness and
regurgitation to increase the personal satisfaction of patients and allow their subsequent
chemotherapy. It is expected that controlled clinical examinations would affirm the clinical
usefulness of the botanicals.

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